Marine-Bioinspired Nanoparticles as Potential Drugs for Multiple Biological Roles

The increased interest in nanomedicine and its applicability for a wide range of biological functions demands the search for raw materials to create nanomaterials. Recent trends have focused on the use of green chemistry to synthesize metal and metal-oxide nanoparticles. Bioactive chemicals have been found in a variety of marine organisms, including invertebrates, marine mammals, fish, algae, plankton, fungi, and bacteria. These marine-derived active chemicals have been widely used for various biological properties. Marine-derived materials, either whole extracts or pure components, are employed in the synthesis of nanoparticles due to their ease of availability, low cost of production, biocompatibility, and low cytotoxicity toward eukaryotic cells. These marine-derived nanomaterials have been employed to treat infectious diseases caused by bacteria, fungi, and viruses as well as treat non-infectious diseases, such as tumors, cancer, inflammatory responses, and diabetes, and support wound healing. Furthermore, several polymeric materials derived from the marine, such as chitosan and alginate, are exploited as nanocarriers in drug delivery. Moreover, a variety of pure bioactive compounds have been loaded onto polymeric nanocarriers and employed to treat infectious and non-infectious diseases. The current review is focused on a thorough overview of nanoparticle synthesis and its biological applications made from their entire extracts or pure chemicals derived from marine sources.


Introduction
Infectious diseases have the potential to contribute to an increase in the global death rate [1]. Infectious diseases can be caused by viruses, fungi, and bacteria [2]. These microorganisms cause a variety of diseases, including cholera, candidiasis, and COVID-19 [3,4]. COVID-19 is a recent example that has triggered a pandemic [5]. Multiple drug resistance in viruses, fungi, and bacteria has reached alarming levels that must be addressed promptly. Various health organizations throughout the world have stated that various drug-resistant pathogenic microorganisms must be eradicated quickly [6]. Furthermore, current drugs for treating infectious diseases to patients suffering from non-infectious illnesses, such as cancer, inflammation, obesity, and diabetes, might possibly harm the human body [7][8][9]. To meet this demand, novel molecules that can function as antimicrobials against pathogenic microbes must be investigated [10]. The terrestrial ecosystem has yet to investigate the

Marine Organisms and Compounds for the Green Synthesis of NPs
Current research and innovation in marine science are contributing to the exponential growth of numerous sectors, including pharmaceuticals, environmental trends, nanomedicine, and food [14]. The ocean covers around 70-71% of the earth's surface [34]. Previous research studied the oceans, accounting for around 2.2 million distinct species [35]. The ocean contains an unimaginable number of marine-derived compounds with varied applications that are beneficial to humans, such as antimicrobial compounds [36]. The marine ecosystem contains around 25,000 physiologically active chemicals with various applications [37]. Currently, the marine environment paves the way for numerous antibacterial, antifungal, and antiviral compounds. Seaweeds, bacteria, and fungus are possible sources for combating infectious diseases [14,38]. According to prior research, the market for marine-derived compounds has surpassed 10 billion USD [39]. The production of marine-based nanoparticles from a variety of sources, including bacteria, fungus, seaweeds, and marine plants, has received considerable attention [33]. Algae with high cell growth rates, high stress tolerance, and an abundance of physiologically active substances, such as Ulva lactuca, Spirulina platensis, and Sargassum muticum, are regarded as promising biocatalysts for the synthesis of various types of nanomaterials [40][41][42]. Among pure algal compounds, phloroglucinol, eckol, phlorofucofuroeckol A, fucodiphlorethol G, 7-phloroeckol, 6,6′-bieckol, and dieckol act as effective reducing agents in the nanoparticle synthesis process [43]. Diverse marine microorganisms adapt to harsh marine environments as well as a broad variety of temperatures, salinity, and pH, making them suitable biological factories for green nanoparticle synthesis [44]. Bacteria and fungi produce intracellular or extracellular inorganic compounds that react with metal ions to form nanoparticles [45,46]. Furthermore, nanoparticles made from marine-derived animals show good biocompatibility [47]. Seafood waste, in particular, may be used to make a variety of biological products by utilizing its high value-added qualities during the purification process [48]. Figure 2 shows numerous pure compounds obtained from marine organisms that act as reducing agents in the nanoparticle synthesis process.

Marine Organisms and Compounds for the Green Synthesis of NPs
Current research and innovation in marine science are contributing to the exponential growth of numerous sectors, including pharmaceuticals, environmental trends, nanomedicine, and food [14]. The ocean covers around 70-71% of the earth's surface [34]. Previous research studied the oceans, accounting for around 2.2 million distinct species [35]. The ocean contains an unimaginable number of marine-derived compounds with varied applications that are beneficial to humans, such as antimicrobial compounds [36]. The marine ecosystem contains around 25,000 physiologically active chemicals with various applications [37]. Currently, the marine environment paves the way for numerous antibacterial, antifungal, and antiviral compounds. Seaweeds, bacteria, and fungus are possible sources for combating infectious diseases [14,38]. According to prior research, the market for marine-derived compounds has surpassed 10 billion USD [39]. The production of marine-based nanoparticles from a variety of sources, including bacteria, fungus, seaweeds, and marine plants, has received considerable attention [33]. Algae with high cell growth rates, high stress tolerance, and an abundance of physiologically active substances, such as Ulva lactuca, Spirulina platensis, and Sargassum muticum, are regarded as promising biocatalysts for the synthesis of various types of nanomaterials [40][41][42]. Among pure algal compounds, phloroglucinol, eckol, phlorofucofuroeckol A, fucodiphlorethol G, 7phloroeckol, 6,6 -bieckol, and dieckol act as effective reducing agents in the nanoparticle synthesis process [43]. Diverse marine microorganisms adapt to harsh marine environments as well as a broad variety of temperatures, salinity, and pH, making them suitable biological factories for green nanoparticle synthesis [44]. Bacteria and fungi produce intracellular or extracellular inorganic compounds that react with metal ions to form nanoparticles [45,46]. Furthermore, nanoparticles made from marine-derived animals show good biocompatibility [47]. Seafood waste, in particular, may be used to make a variety of biological products by utilizing its high value-added qualities during the purification process [48]. Figure 2 shows numerous pure compounds obtained from marine organisms that act as reducing agents in the nanoparticle synthesis process.  Table 1 summarizes a detailed review of marine-based nanoparticles utilized in treating various infectious diseases. Bacterial infection has a negative impact on public health [49]. Nanoparticles are attractive options since they have excellent bactericidal activity when treating pathogenic bacteria [50]. Several studies have been carried out to investigate the mechanisms of marine-inspired nanoparticles as antibacterial agents [51]. In general, marine antimicrobial macromolecules exhibit antibacterial mechanisms, such as (1) inhibition of DNA replication, (2) inhibition of expression of enzymes and other cellular proteins required for ATP production, (3) structural changes and damage to bacterial cell membranes, and (4) ROS production by inhibiting respiratory enzymes [52]. Several marine bacteria, including Vibrio spp., Pseudoalteromonas spp., and Ruegeria spp., generate antimicrobial compounds, a feature seen globally [53]. The marine bacterium Pseudomonas rhizosphaerae, in particular, has been shown to produce benzene-type secondary metabolites with potent antibacterial properties [54]. Secondary metabolites produced by marine algae, on the other hand, include polyphenols, terpenes, acetogenin, and aromatic compounds, which have a variety of biological functions, including antibacterial effects [55]. Silver nanoparticles derived from the marine cyanobacterium Chroococcus minutus showed antibacterial action against pathogenic strains of Escherichia coli and Streptococcus pyogenes, which have been discovered to be novel antibacterial for upper respiratory tract infection [56]. The synthesis of silver nanoparticles from cyanobacterium sources had improved control over pathogenic bacteria. Silver nanoparticles derived from the marine endophytic fungus Penicillium polonicum showed antibacterial activity against Acinetobacter baumanii, with MIC value of 15.62 µg/mL and MBC value of 31.24 µg/mL [44]. These findings were attributed to the activation of apoptosis by altering the osmotic pressure regulation of cells during the interaction of silver nanoparticles and bacteria. Silver nanoparticles using S. muticum extracts as a capping agent significantly suppressed the growth of Bacillus subtilis, E. coli, Klebsiella pneumoniae, and Salmonella Typhimurium [57]. These  Table 1 summarizes a detailed review of marine-based nanoparticles utilized in treating various infectious diseases. Bacterial infection has a negative impact on public health [49]. Nanoparticles are attractive options since they have excellent bactericidal activity when treating pathogenic bacteria [50]. Several studies have been carried out to investigate the mechanisms of marine-inspired nanoparticles as antibacterial agents [51]. In general, marine antimicrobial macromolecules exhibit antibacterial mechanisms, such as (1) inhibition of DNA replication, (2) inhibition of expression of enzymes and other cellular proteins required for ATP production, (3) structural changes and damage to bacterial cell membranes, and (4) ROS production by inhibiting respiratory enzymes [52]. Several marine bacteria, including Vibrio spp., Pseudoalteromonas spp., and Ruegeria spp., generate antimicrobial compounds, a feature seen globally [53]. The marine bacterium Pseudomonas rhizosphaerae, in particular, has been shown to produce benzene-type secondary metabolites with potent antibacterial properties [54]. Secondary metabolites produced by marine algae, on the other hand, include polyphenols, terpenes, acetogenin, and aromatic compounds, which have a variety of biological functions, including antibacterial effects [55]. Silver nanoparticles derived from the marine cyanobacterium Chroococcus minutus showed antibacterial action against pathogenic strains of Escherichia coli and Streptococcus pyogenes, which have been discovered to be novel antibacterial for upper respiratory tract infection [56]. The synthesis of silver nanoparticles from cyanobacterium sources had improved control over pathogenic bacteria. Silver nanoparticles derived from the marine endophytic fungus Penicillium polonicum showed antibacterial activity against Acinetobacter baumanii, with MIC value of 15.62 µg/mL and MBC value of 31.24 µg/mL [44]. These findings were attributed to the activation of apoptosis by altering the osmotic pressure regulation of cells during the interaction of silver nanoparticles and bacteria. Silver nanoparticles using S. muticum extracts as a capping agent significantly suppressed the growth of Bacillus subtilis, E. coli, Klebsiella pneumoniae, and Salmonella Typhimurium [57]. These silver nanoparticles interacted with the bacterial membrane and penetrated the bacterium. Moreover, silver nanoparticles synthesized using S. swartzii showed antibacterial action by producing considerable deteri-oration in E. coli [58]. When combined with silver nanoparticles, S. wightii and Valonopsis pachynema demonstrated increased antibacterial activity against Micrococcus luteus and S. marcescens [59]. Silver nanoparticles produced from these seaweeds had a strong antibacterial activity because silver ions caused bacteria to release K + ions. Silver nanoparticles produced from an aqueous extract of Gelidiella acerosa inhibited the growth of P. aeruginosa and B. subtilis [60]. These bacteria were discovered to absorb silver nanoparticles from the cell surface. Silver nanoparticles produced using a culture-free extract of marine Streptomyces sp. Al-Dhabi-87 had excellent antibacterial activity against wound-infecting microorganism strains such as Staphylococcus aureus, S. epidermidis, and Enterococcus faecalis [61]. These nanoparticles displayed antibacterial action by releasing intracellular components and altering the cellular structure. Secondary metabolites found in S. longifolium extract reduced CuSO 4 to Cu 2+ , resulting in copper oxide nanoparticles [62]. These CuSO 4 nanoparticles showed remarkable antibacterial activity against V. parahemolyticus, V. harvey, Aeromonas hydrophila, and Serratia marcescens.

Marine Bioinspired NPs Used for Bacterial Infection
Carrageenan is a water-soluble, high-molecular-weight, sulfated polysaccharide isolated from many species of red algae. Carrageenan has been widely used in the pharmaceutical, medical, and food industries due to its high viscosity, gelling capacity, and biocompatibility [63,64]. Vijayakumar et al. [65] synthesized Kappa-carrageenan wrapped zinc-oxide nanoparticles (KC-ZnONPs) with antibacterial and antibiofilm activity against Methicillin-resistant S. aureus (MRSA) ( Figure 3). Based on hemocompatibility studies on human RBCs and eco-safety studies using Artemia salina, the synthesized KC-ZnONPs showed high biocompatibility and were non-toxic to the environment.
Fucoidan, a pure chemical derived from Fucus vesiculosus, was used to synthesize gold nanoparticles, which demonstrated antibacterial action against P. aeruginosa (MIC value of 512 µg/mL) [66]. In addition, the fucoidan-gold nanoparticles reduced the production of virulence factors, such as rhamnolipid, pyocyanin, and pyoverdine. Due to the presence of mannose, the capsular polymeric material isolated from marine B. altitudinis proved efficient as a stabilizer for CuO nanoparticle synthesis [67]. The MIC value of CuO nanoparticles containing mannose against P. aeruginosa was 1.0 µg/mL. Silver nanoparticles synthesized by the marine fungus Aspergillus flavus utilizing amylase showed antibacterial efficacy against Gram-positive and Gram-negative bacteria [68]. In particular, amylasesilver nanoparticles had the strongest antibacterial activity against A. hydrophila (MIC value of 1.6 µg/mL). Khan et al. [69] synthesized gold nanoparticles from chitosan oligosaccharide, a natural marine compound, to treat P. aeruginosa biofilm infections. Chitosan oligosaccharide-gold nanoparticles exhibited antibiofilm efficacy by lowering bacterial hemolysis and P. aeruginosa virulence factors. P. aeruginosa hemolysis and protease activity were reduced by a nanocomposite of chitosan and polypyrrole [70]. Moreover, the production of various virulence factors, such as rhamnolipid, pyoverdine, and pyocyanin was reduced by this nanocomposite.

Marine Bioinspired NPs Used for Fungal Infection
Fungal infection is a constant cause of death [71]. The number of fungal infection cases is increasing, and it has been claimed that over 150 million fungal infections occur yearly, with a 1.5 million death rate from fungal infection [72]. Several secondary metabolites with antifungal action are produced by marine microorganisms, mammals, and algae, similar to antibacterial activity [73]. Antifungal chemicals are produced by a variety of marine species, including bacterial chitinases, lipopeptides, and lactones [74]. Brown algae phlorotannins, on the other hand, have antifungal activity by altering the composition of ergosterol in the yeast cell membrane [75]. The marine depsipeptidepapuamide A has been shown to trigger fungus apoptosis by binding to phosphatidylserine in the cell membrane and entering the plasma membrane [76]. Plakortide F acid, a polyketide endoperoxide produced from marine sponges, also had antifungal activity through affecting Ca 2+ homeostasis [77]. As a result, many researchers continue to look for antifungal activity in a variety of marine organisms for application to nanoparticles. Green synthesis of silver nanoparticles from U. rigida had antifungal action against the fungus Trichophyton mantigrophytes and T. cutaneum, which are linked toskin infections [78].

Marine Bioinspired NPs Used for Fungal Infection
Fungal infection is a constant cause of death [71]. The number of fungal infection cases is increasing, and it has been claimed that over 150 million fungal infections occur yearly, with a 1.5 million death rate from fungal infection [72]. Several secondary metabolites with antifungal action are produced by marine microorganisms, mammals, and algae, similar to antibacterial activity [73]. Antifungal chemicals are produced by a variety of marine species, including bacterial chitinases, lipopeptides, and lactones [74]. Brown algae phlorotannins, on the other hand, have antifungal activity by altering the composition of ergosterol in the yeast cell membrane [75]. The marine depsipeptidepapuamide A has been shown to trigger fungus apoptosis by binding to phosphatidylserine in the cell membrane and entering the plasma membrane [76]. Plakortide F acid, a polyketide endoperoxide produced from marine sponges, also had antifungal activity through affecting Ca 2+ homeostasis [77]. As a result, many researchers continue to look for antifungal activity in a variety of marine organisms for application to nanoparticles. Green synthesis of silver nanoparticles from U. rigida had antifungal action against the fungus Trichophyton mantigrophytes and T. cutaneum, which are linked toskin infections [78]. These silver nanoparticles produced an insoluble chemical that inactivated the fungal cell wall's sulfhydryl group and disrupted the membrane, resulting in an antifungal effect. Silver nanoparticles synthesized from aqueous extracts of Cymodocea serrulata and Padina australis had antifungal action against plant fungi, including Pyriporia oryzea, Alternaria sp., Helminthisporium oryzea, Rhizoctonia solani, and Xanthomanas oryzae [104]. These antifungals were discovered as a consequence of cell wall disruption, DNA damage, and an increase in ROS. Silver nanoparticles (AgNPs) synthesized from Gelidium corneum extract, which served as a reducing agent had excellent antifungal and antibiofilm properties against Candida albicans [83]. Biosynthetic silver nanoparticles, in particular, demonstrated antifungal effectiveness by generating cell membrane and cell wall destruction, as well as cytoplasmic damage (Figure 4). These silver nanoparticles produced an insoluble chemical that inactivated the fungal cell wall's sulfhydryl group and disrupted the membrane, resulting in an antifungal effect. Silver nanoparticles synthesized from aqueous extracts of Cymodocea serrulata and Padina australis had antifungal action against plant fungi, including Pyriporia oryzea, Alternaria sp., Helminthisporium oryzea, Rhizoctonia solani, and Xanthomanas oryzae [104]. These antifungals were discovered as a consequence of cell wall disruption, DNA damage, and an increase in ROS. Silver nanoparticles (AgNPs) synthesized from Gelidium corneum extract, which served as a reducing agent had excellent antifungal and antibiofilm properties against Candida albicans [83]. Biosynthetic silver nanoparticles, in particular, demonstrated antifungal effectiveness by generating cell membrane and cell wall destruction, as well as cytoplasmic damage (Figure 4).

Marine Bioinspired NPs for Treating Viral Infection
A viral particle is smaller than a live cell. Several viral infections have been documented to be caused by a pathogenic virus. Viruses cause a variety of diseases, leading to increased death rate. Viral infections include smallpox, polio, HIV, and hepatitis C [105]. Antiviral compounds produced by marine organisms include polyphenols, alkaloids, lipids, carbohydrates, steroids, terpenoids, exopolysaccharides, polyketides, zoanthoxanthins, and peptides [106]. Virus adsorption, penetration, capsid decoration, biosynthesis, virus assembly, and virus release are all inhibited or inactivated by marine polysaccharides [107]. One of the metabolites produced by marine organisms, phlorotannins, has been shown to interfere with viral attachment, penetration, and replication [15]. Silver nanoparticles derived from the seaweed U. lactuca showed cytotoxic efficacy against the

Marine Bioinspired NPs for Treating Viral Infection
A viral particle is smaller than a live cell. Several viral infections have been documented to be caused by a pathogenic virus. Viruses cause a variety of diseases, leading to increased death rate. Viral infections include smallpox, polio, HIV, and hepatitis C [105]. Antiviral compounds produced by marine organisms include polyphenols, alkaloids, lipids, carbohydrates, steroids, terpenoids, exopolysaccharides, polyketides, zoanthoxanthins, and peptides [106]. Virus adsorption, penetration, capsid decoration, biosynthesis, virus assembly, and virus release are all inhibited or inactivated by marine polysaccharides [107]. One of the metabolites produced by marine organisms, phlorotannins, has been shown to interfere with viral attachment, penetration, and replication [15]. Silver nanoparticles derived from the seaweed U. lactuca showed cytotoxic efficacy against the vector-borne pathogens Aedes aegypti and Culex pipiens [79]. Because of their small particle size, silver nanoparticles synthesized from U. lactuca demonstrated more effective action than conventional insecticides. Additionally, these silver nanoparticles bonded to the insect cuticle and entered within the cell, disrupting additional cell functions. Silver nanoparticles mediated by Oscillatoria sp. and gold nanoparticles mediated by S. platensis displayed antiviral efficacy against herpesvirus [100]. These nanoparticles induced glycoprotein aggregation and surface changes, both of which might inhibit viral binding and penetration. Silver nanoparticles derived from extracellular extracts of the marine actinomycetes Rhodococcus rhodochrous and Streptomyces sp. inhibited poliovirus in RD cells [85]. The interaction of viral proteins with silver nanoparticles caused poliovirus inhibition. Silver nanoparticles derived from Dictyosphaerium sp., a freshwater microalgae, had substantial antiviral activity against the Newcastle disease virus [101]. These silver nanoparticles were bound to the viral glycoprotein envelope, limiting virus penetration. Table 2 shows studies that have used marine bioinspired nanoparticles to treat a wide range of non-infectious diseases. Inflammation is the body's natural response to tissue injury, infection, and genetic alterations [108]. The immune system is activated within the body under inflammatory circumstances, resulting in the release of various inflammatory mediators, such as bradykinins and prostaglandins [109]. Thus, reducing prostaglandin levels can aid in the prevention of chronic disease by controlling inflammation [110]. To reduce inflammation and inflammatory mediators, steroids and nonsteroidal antiinflammatory medications constitute one of the treatment paths for inflammatory diseases [111]. These synthetic antiinflammatory drugs, on the other hand, can have substantial negative effects [112]. As a result, it is required to use marine-based organisms with high biological activity to generate nanoparticles with similar therapeutic benefits and no negative effects. Silver nanoparticles produced from macroalgae such as Galaxaura elongate, Turbinaria ornate, and Enteromorpha flexuosa have shown considerable antiinflammatory action via membrane stabilization [113]. Silver nanoparticles, in particular, reduced prostaglandin production by inhibiting protein denaturation, cyclooxygenase, and 5-lipoxygenase. At 500 µg/mL, ZnO nanoparticles wrapped in Kappa-carrageenan demonstrated 82% antiinflammatory efficacy ( Figure 3) [65]. Because of their high surface area to volume ratio, these nanoparticles were more effective than bulk materials in inhibiting cytokines and inflammatory coenzymes. Cancer is caused by the uncontrollable growth of cells and tissues [114]. Cancer treatment options include surgery, radiation, and potentially toxic medication therapy [115]. As a result, several investigations are being done to discover anticancer drugs that kill cancer cells without hurting humans [116]. Nanoparticles loaded with various physiologically active chemicals are one of the most effective drug delivery techniques for cancer therapy [117]. Marine-derived natural products, in particular, are potential molecules for the development of anticancer drugs because they may influence multiple pathways, such as immunity, cancer cell death, and tumor growth [118]. Silver nanoparticles derived from Caulerpa taxifolia showed antitumor efficacy against A549 lung cancer cells [119]. Necrosis and condensation of A549 cells were shown to be mediated by silver nanoparticles derived from marine algae, suggesting that nanomaterials are relevant for cancer cell research. Furthermore, gold nanoparticles inhibited phosphorylation of AKT and ERK, which are essential for cell growth in HeLa cancer cells [47]. Interestingly, these gold nanoparticles derived from jellyfish extract exhibited a significant lethal effect on HeLa cancer cells. Cu 2 O nanoparticles derived from Rhodotorula mucilaginosa showed anticancer activity against SKOV-3, MCF-7, HepG2, A549, SW620, and HT-29 [117]. In particular, reactive oxygen species production and oxidative stress enhanced the anticancer mechanism of Cu 2 O nanoparticles. Similarly, Shunmugam et al. [120] synthesized gold nanoparticles from the marine bacterium V. alginolyticus, which had antioxidant and anticancer activity ( Figure 5). The anticancer activity was attributed to the treated cells' nuclear condensation.    Silver nanoparticles derived from shrimp shell chitin acted as a reducing agent and had anticancer action against human hepatocarcinoma [129]. In HepG2 cells, chitin-silver nanoparticles increased the expression of apoptosis-related proteins Bax, PARP, cytochrome-c, caspase-3, and caspase-9, while decreasing the expression of antiapoptosis proteins Bcl-2 and Bcl-xl. Phloroglucinol-encapsulated starch biopolymer exhibited dose-dependent anticancer activities against the HepG2 liver cancer cell line [130]. These findings were ascribed to the biopolymer's hydrophobicity, which increased adhesion and adsorption capability to the cancer cell surface.

Marine Bioinspired NPs for Treating Non-Infectious Diseases
Cells produce potentially harmful ROS as a result of oxygen metabolism, which involves enzymatic and non-enzymatic reactions [131]. High levels of ROS caused by oxidative stress induce a variety of diseases in the body, including diabetes, hypertension, and Alzheimer's [132]. Antioxidants, on the other hand, have a role in delaying, regulating, and avoiding the oxidative process that leads to the beginning and progression of the Silver nanoparticles derived from shrimp shell chitin acted as a reducing agent and had anticancer action against human hepatocarcinoma [129]. In HepG2 cells, chitin-silver nanoparticles increased the expression of apoptosis-related proteins Bax, PARP, cytochromec, caspase-3, and caspase-9, while decreasing the expression of antiapoptosis proteins Bcl-2 and Bcl-xl. Phloroglucinol-encapsulated starch biopolymer exhibited dose-dependent anticancer activities against the HepG2 liver cancer cell line [130]. These findings were ascribed to the biopolymer's hydrophobicity, which increased adhesion and adsorption capability to the cancer cell surface.
Cells produce potentially harmful ROS as a result of oxygen metabolism, which involves enzymatic and non-enzymatic reactions [131]. High levels of ROS caused by oxidative stress induce a variety of diseases in the body, including diabetes, hypertension, and Alzheimer's [132]. Antioxidants, on the other hand, have a role in delaying, regulating, and avoiding the oxidative process that leads to the beginning and progression of the disease [133]. Through SOD enzymes, which catalyze the recombination of oxygen radicals, these antioxidants counteract the consequences of oxidative stress [134]. Currently, research is being performed to investigate natural substances capable of controlling oxidative stress, which leads to the investigation of nanoparticles with antioxidant activities. Many species with antioxidant activity in marine organisms, in particular, have been found and have piqued the interest of researchers due to their potential biological activity [135]. The antioxidant activity of gold nanoparticles produced by the marine fungus A. chlamydospora (inhibition of DPPH radicals) was dose-dependent [125]. Furthermore, in a concentrationdependent way, gold nanoparticles mediated by the marine bacteria Paracoccus haeundaensis cell-free supernatant demonstrated strong reducing power via DPPH scavenging activity [128]. Selenium nanoparticles produced from Spirulina phycocyanin protected INS-1E rat insulinoma cells against palmitic acid-induced cell death [136]. Phycocyanin and selenium shielded cells from oxidative damage and signaling pathways downstream. These findings indicate that marine-derived nanoparticles can be employed as effective natural antioxidants. Figure 6 depicts the biological activity of nanoparticles synthesized using phloroglucinol. Silver nanoparticles synthesized using phloroglucinol showed anticancer efficacy against the MCF-7 breast cancer cell line [137]. Silver ions from phloroglucinol silver nanoparticles entered cancer cells and interacted with intracellular macromolecules, such as organelles, proteins, and DNA, to trigger apoptosis. Another study found that phloroglucinolgold nanoparticles triggered death in HeLa cancer cells via enhancing mitochondrial membrane permeability [138]. Phloroglucinol-encapsulated chitosan nanoparticles showed antibiofilm action against single-species biofilms, such as K. pneumoniae, S. aureus, S. mutans, and C. albicans, and mixed-species biofilms, such as C. albicans-S. aureus/K. pneumoniae/S. mutans [139]. Gold and zinc oxide nanoparticles produced with phloroglucinol showed significant antibacterial action against P. aeruginosa [140]. Moreover, these nanoparticles inhibited P. aeruginosa twitching, swimming, and swarming motility, all of which have virulence features. Similarly, several marine-derived pure compounds are employed in synthesizing nanoparticles and encapsulating drugs for application in the field of medicine (Table 3).  [137]. (B) Synthesis of the phloroglucinol-conjugated gold nanoparticles, which exhibit therapeutic potential towards cancer cells. The action mechanism involved apoptosis of cancer cells by promoting mitochondrial transmembrane permeation, as evident by fluorescence staining and gene expression studies. Reprinted with permission from reference [138], (C) Encapsulation of phloroglucinol into the chitosan nanoparticles. The PG-CSNPs exhibit antibiofilm properties towards single-and mixed-species biofilms of C. albicans-S. aureus/S. mutans/K. penumoniae. Reprinted with permission from reference [139], and (D) Synthesis of metal (AuNPs) and metal oxide (ZnONPs) nanoparticles using phloroglucinol. The synthesized PG-AuNPs and PG-ZnONPs showed antibiofilm and antivirulence properties towards P. aeruginosa. Reproduced with permission from reference [140]. Copyright 2021 by the authors and licensee MDPI, Basel, Switzerland.  [137]. (B) Synthesis of the phloroglucinol-conjugated gold nanoparticles, which exhibit therapeutic potential towards cancer cells. The action mechanism involved apoptosis of cancer cells by promoting mitochondrial transmembrane permeation, as evident by fluorescence staining and gene expression studies. Reprinted with permission from reference [138], (C) Encapsulation of phloroglucinol into the chitosan nanoparticles. The PG-CSNPs exhibit antibiofilm properties towards single-and mixed-species biofilms of C. albicans-S. aureus/S. mutans/K. penumoniae. Reprinted with permission from reference [139], and (D) Synthesis of metal (AuNPs) and metal oxide (ZnONPs) nanoparticles using phloroglucinol. The synthesized PG-AuNPs and PG-ZnONPs showed antibiofilm and antivirulence properties towards P. aeruginosa. Reproduced with permission from reference [140]. Copyright 2021 by the authors and licensee MDPI, Basel, Switzerland. Table 3. Application of marine-derived compounds in the synthesis of nanoparticles and encapsulation of drugs for application in the field of medicine.

Conclusions and Future Perspectives
In conclusion, because of their potential biological activity, marine-derived products have been widely used in the pharmaceutical industry. With an increased understanding of their biological functions, various marine-derived compounds have been used in the synthesis of nanoparticles. These products comprised polymers, organic compounds, and extract, which act as a powerful reducing agent in synthesizing metal and metal-oxide nanoparticles. Furthermore, certain polymeric material is used to effectively deliver the drug in the treatment of infectious and non-infectious diseases. The review detailed the list of the marine organism from which the extract was extracted and which was used to synthesize several forms of nanoparticles. Furthermore, these nanoparticles have been shown to have antimicrobial properties against bacterial, fungal, and viral pathogens. Antimicrobial mechanisms include the breakdown of cell membranes, as well as damage to cell walls and DNA. These marine-inspired nanoparticles have also shown promise in the treatment of non-infectious diseases, such as diabetes, cancer, wounds, inflammatory reactions, and leishmanial infections. Though significant progress has been made in the production of nanoparticles utilizing extracts from marine sources, relatively little information is known on the synthesis of nanoparticles using pure active compounds. This is because of the fact that there are several variations in extract preparation due to a number of environmental factors. As a result, future research should prioritize the use of pure active compounds for nanoparticle synthesis. Most antimicrobial research involving these nanoparticles has been conducted at the phenotypic level; however, investigations at the gene level are highly needed to explain the molecular mechanism.