Search Results (82)

Polymer nanoparticles have been widely studied for tumor treatment due to their excellent biocompatibility, structural diversity, and multi-functionality. Among their various applications, combining polymer-based photosensitizers with photodynamic therapy (PDT) and immunotherapy has emerged as a promising strategy for treating solid tumors. This combination not only enhances local tumor ablation but also activates systemic antitumor immune responses. Polymer Nanoparticles, with their unique photodynamic properties and ability to integrate multiple therapeutic modalities, offer a powerful platform for photo-immunotherapy. This review systematically discusses recent advances in the design of polymer Nanoparticles and their synergistic mechanisms when combined with immunomodulatory agents such as Toll-like receptor (TLR) agonists, STING agonists, and immune checkpoint inhibitors (ICBs). Moreover, we highlight challenges faced in clinical translation and outline future perspectives for the development of these combination therapies. Full article

Silica nanoparticles (SiNPs) are widely explored as biocompatible platforms for the delivery of photosensitizers in photodynamic therapy (PDT). In this work, porphyrins bearing amine (PNH₂) or carboxyl (PCOOH) groups were covalently conjugated onto functionalized SiNP surfaces via carbodiimide-mediated amide coupling, yielding the silica–porphyrin nanohybrids H-PNH₂ and H-PCOOH. Successful surface functionalization was confirmed by Fourier-transform infrared spectroscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy. Photophysical studies demonstrated that both nanohybrids retained efficient singlet oxygen (¹O₂) generation. In vitro biological assays revealed a strong dependence of photodynamic activity on the nature of the conjugated porphyrin, with H-PCOOH exhibiting markedly enhanced photocytotoxicity with respect to the free porphyrins, while H-PNH₂ showed an attenuated light-dose response. Notably, H-PCOOH induced pronounced cell death at low light doses (1 J/cm²), with a half-maximal inhibitory concentration (IC₅₀) below 0.3 µM. These findings highlight the potential of silica–porphyrin nanohybrids as efficient photosensitizers for PDT applications. Full article

Photodynamic therapy (PDT) is a promising localized strategy for the treatment of cervical cancer, ranking as the fourth most common cancer among women worldwide. The integration of photosensitizers (PSs) in localized drug delivery systems (DDSs), particularly in electrospun nanofibers, holds tremendous potential to overcome the drawbacks of their systemic administration. Exploring multilayer fibrous architectures provides a versatile therapeutic platform to design the next generation of localized DDS. In this work, localized implants for cancer treatment using PDT were developed using polyhydroxyalkanoate (PHA), chitosan (CS) and polyethylene oxide (PEO) as biopolymers and a porphyrin (Por) as PS, following two approaches: blended PHA/Por electrospun microfibers and multilayered membranes (PHA–Por/CS/PEO) produced by sequential electrospinning. The synthesized Por displayed higher cytotoxicity in light compared to dark against tumor cells. All the developed membranes were characterized regarding their morphology, wettability, absorption and fluorescence properties. PHA–Por membranes exhibited overall uniform fibrous morphologies with successful Por incorporation. Nonetheless, they presented a highly hydrophobic surface, compromising the Por release and cell–material interactions. In contrast, multilayer PHA–Por/CS/PEO membranes demonstrated enhanced hydrophilicity and enabled sustained Por release. Upon light irradiation, these membranes induced a significantly greater inhibition of HeLa cell proliferation (29.61%) compared to dark conditions (6.21%), confirming their photodynamic activity. Full article

Background/Objectives: Aberrant metabolism in tumors exacerbates the immunosuppressive tumor microenvironment. The immunosuppressive metabolite kynurenine inhibits the activation of effector T cells. Current antitumor drugs targeting kynurenine focus on small molecule inhibitors, which exhibit suboptimal efficacy in suppressing kynurenine generation owing to the diversity of kynurenine synthesis pathways. In contrast, kynureninase (KYNase) can directly metabolize kynurenine regardless of the production source. However, its delivery is hindered by short blood-circulation half-life and poor tumor accumulation. Additionally, photodynamic therapy (PDT) has been reported to synergize with immunotherapy, suggesting a potential combinatorial photodynamic immunometabolic cancer therapy with KYNase. Methods: A KYNase-Fc fusion protein was prepared to prolong blood circulation and enhance tumor accumulation of KYNase. Meanwhile, KYNase-Fc served as a nanocarrier for photosensitizer pheophorbide A (PhA) due to the high binding affinity between KYNase-Fc and PhA. Through self-assembly, KYNase-Fc/PhA nanoparticles (KYNase-Fc/PhA NPs) were prepared without extra carrier materials. Results: Compared with the PEGylated KYNase, KYNase-Fc exhibited significantly prolonged blood circulation, enhanced tumor accumulation and effective tumor suppression. Moreover, the prepared KYNase-Fc/PhA NPs facilitated rapid PhA tumor accumulation. The combined photodynamic immunometabolic therapy alleviated the immunosuppressive microenvironment and significantly inhibited the growth of subcutaneous 4T1 tumors in mice. Conclusions: KYNase-Fc offered a carrier-free nanomedicine for co-delivery of PhA for photodynamic immunometabolic antitumor therapy with enhanced efficacy, providing a promising platform for clinical translation. Full article

Breast cancer remains the most common and leading cause of cancer deaths among women worldwide. The efficacy of conventional therapies is often hampered by off-target effects and multidrug resistance. Phototherapy, encompassing photodynamic therapy (PDT) and photothermal therapy (PTT), has gained significant attention due to its non-invasiveness, high spatiotemporal selectivity, and minimal side effects. However, its application is hindered by several obstacles, including the tumor hypoxic microenvironment, insufficient light penetration depth, and acquired heat resistance. Metal–organic frameworks (MOFs) have adjustable structures, enormous specific surfaces, and facile functionalization, providing an ideal platform to overcome these limitations. This review summarizes the latest research progress in the application of MOFs for precision phototherapy in breast cancer treatment. It emphasizes their role as a direct photosensitizer (PS), photothermal agent (PTA), or multifunctional nanocarrier for PDT, PTT, and synergistic phototherapy (including PDT/PTT, chemo/phototherapy, and immunotherapy/phototherapy). The design strategy and therapeutic effect of MOFs for phototherapy of breast cancer are critically discussed. In addition, the current bottlenecks and future perspectives are outlined to facilitate the clinical translation of MOF-based breast cancer treatment platforms. Full article

Photodynamic therapy (PDT) is an established light-based treatment modality that relies on the activation of photosensitizers to generate reactive oxygen species (ROS) and induce localized cytotoxicity. In recent years, microalgae have emerged as a promising and sustainable source of natural photosensitizers due to their ability to biosynthesize structurally diverse pigments with strong light-harvesting capacity. This review provides a comprehensive, application-oriented analysis of microalgae-derived photosensitizers, focusing on chlorophylls and their derivatives, carotenoids, and phycobiliproteins. Particular attention is given to analytical strategies for pigment extraction, purification, and characterization, as well as to photophysical properties, subcellular localization, and ROS-mediated mechanisms underlying photodynamic activity. Recent advances in the chemical modification of algal pigments, including chlorin-based derivatives and 5-aminolevulinic acid–related systems, are critically discussed in relation to structure–activity relationships and translational performance. The accumulated evidence demonstrates that microalgae-derived pigments and their synthetic analogues can achieve efficient singlet oxygen generation, organelle-specific phototoxicity, and favorable therapeutic selectivity. Taken together, these findings highlight microalgae as a renewable and versatile platform for developing next-generation photosensitizers with broad biomedical potential in oncology, dermatology, and antimicrobial photodynamic therapy. Full article

Biomolecule–photosensitizer conjugates have rapidly evolved into one of the most powerful strategies for improving the selectivity, efficacy, and translational potential of photodynamic therapy (PDT). By integrating photosensitizers (PSs) with carbohydrates, amino acids, peptides, aptamers, proteins, cofactors, vitamins or antibodies, these constructs overcome long-standing limitations of classical PDT, including poor solubility, insufficient tumour accumulation, and strong dependence on oxygen availability. Beyond enhancing receptor-mediated uptake and enabling precise interactions with the tumour microenvironment (TME), bioconjugation also modulates aggregation, photochemical properties, intracellular accumulation, and immune system activation. A particularly transformative trend is the emergence of supramolecular architectures in which photosensitizers form defined nanostructured aggregates with peptides or proteins. Once considered an undesirable phenomenon, aggregation is now recognized as a tenable feature that governs photochemical behaviour. Engineered aggregates can undergo environment-triggered disassembly to monomeric, photoactive states, or operate as semiconductor-like nanodomains capable of Type I reaction through symmetry-breaking charge separation. This shift toward oxygen-independent radical pathways offers a promising solution to the challenge of hypoxia, a hallmark of the TME that severely compromises conventional Type II PDT. Parallel advances in 3D experimental platforms such as tumour organoids and organ-on-chip systems provide physiologically relevant validation of these conjugates, enabling the assessment of penetration, subcellular localization, immunogenic cell death, and therapeutic synergy within realistic TME conditions. Collectively, the integration of biomolecular targeting with controlled supramolecular design is redefining the landscape of PDT. Future progress will depend on designing conjugates that retain high activity under hypoxia, engineering dynamic aggregate states, and systematically validating these systems in advanced TME-mimetic models. Together, these developments position biomolecule–photosensitizer conjugates as a versatile and increasingly less oxygen-dependent class of next-generation phototherapeutic agents. Full article

Background/Objectives: Boron-dipyrromethene (BODIPY) derivatives are a superior class of fluorophores prized for their exceptional photostability and tunable photophysical properties. While ideal for imaging, their translation to photodynamic therapy (PDT) has been hampered by excitation in the visible range, leading to poor tissue penetration. To overcome this, intense research has focused on developing near-infrared (NIR)-absorbing BODIPY photosensitizers (PS). This review aims to systematically summarize the hierarchical design strategies, from molecular engineering to advanced nanoplatform construction, that underpin the recent progress of NIR-BODIPY PS in therapeutic applications. Methods: We conducted a comprehensive literature review using PubMed, Scopus, and Web of Science databases. The search focused on keywords such as “BODIPY”, “aza-BODIPY”, “near-infrared”, “photodynamic therapy”, “photothermal therapy”, “nanocarriers”, “hypoxia”, “immuno-phototherapy”, and “antibacterial.” This review analyzes key studies describing molecular design, chemical modification strategies (e.g., heavy-atom effect, π-extension), nanoplatform formulation, and therapeutic applications in vitro and in vivo. Results: Our analysis reveals a clear progression in design complexity. At the molecular level, we summarize strategies to enhance selectivity, including active targeting, designing “smart” PS responsive to the tumor microenvironment (TME) (e.g., hypoxia or low pH), and precise subcellular localization (e.g., mitochondria, lysosomes). We then detail the core chemical strategies for achieving NIR absorption and high singlet oxygen yield, including π-extension, the internal heavy-atom effect, and heavy-atom-free mechanisms (e.g., dimerization). The main body of the review categorizes the evolution of advanced theranostic nanoplatforms, including targeted systems, stimuli-responsive ‘smart’ systems, photo-immunotherapy (PIT) platforms inducing immunogenic cell death (ICD), hypoxia-overcoming systems, and synergistic chemo-phototherapy carriers. Finally, we highlight emerging applications beyond oncology, focusing on the use of NIR-BODIPY PS for antibacterial therapy and biofilm eradication. Conclusions: NIR-BODIPY photosensitizers are a highly versatile and powerful class of theranostic agents. The field is rapidly moving from simple molecules to sophisticated, multifunctional nanoplatforms designed to overcome key clinical hurdles like hypoxia, poor selectivity, and drug resistance. While challenges in scalability and clinical translation remain, the rational design strategies and expanding applications, including in infectious diseases, confirm that NIR-BODIPY derivatives will be foundational to the next generation of precision photomedicine. Full article

Breast cancer is one of the most prevalent malignant tumors worldwide, with the highest incidence and mortality among women. Early precise diagnosis and the development of efficient treatment regimens remain major clinical challenges. Harnessing the programmable size, surface chemistry, and tumor microenvironment (TME) responsiveness of nanomaterials, there is tremendous potential for their applications in breast cancer diagnosis and therapy. In the diagnostic arena, nanomaterials serve as core components of novel contrast agents (e.g., gold nanorods, quantum dots, superparamagnetic iron oxide nanoparticles) and biosensing platforms, substantially enhancing the sensitivity and specificity of molecular imaging modalities—such as magnetic resonance imaging (MRI), computed tomography (CT), and fluorescence imaging (FLI)—and enabling high-sensitivity detection of circulating tumor cells and tumor-derived exosomes, among various liquid biopsy biomarkers. In therapy, nanoscale carriers (e.g., liposomes, polymeric micelles) improve tumor targeting and accumulation efficiency through passive and active targeting strategies, thereby augmenting anticancer efficacy while effectively reducing systemic toxicity. Furthermore, nanotechnology has spurred the rapid advancement of emerging modalities, including photothermal therapy (PTT), photodynamic therapy (PDT), and immunotherapy. Notably, the construction of theranostic platforms that integrate diagnostic and therapeutic units within a single nanosystem enables in vivo, real-time visualization of drug delivery, treatment monitoring, and therapeutic response feedback, providing a powerful toolkit for advancing breast cancer toward personalized, precision medicine. Despite challenges that remain before clinical translation—such as biocompatibility, scalable manufacturing, and standardized evaluation—nanomaterials are undoubtedly reshaping the paradigm of breast cancer diagnosis and treatment. Full article

Gold nanoparticles (AuNPs) synthesized via picosecond pulsed laser ablation were investigated as enhancers of methylene blue (MB)-mediated photodynamic therapy (PDT) against Escherichia coli. AuNPs produced at 532 and 1064 nm with frequencies of 20–50 kHz showed frequency- and size-dependent effects, with 50 kHz yielding the highest particle concentrations and smaller particles enhancing reactive oxygen species (ROS) generation. UV-Vis and fluorescence spectroscopy confirmed nanoparticle formation and plasmonic properties consistent with TEM measurements. Photobleaching assays demonstrated that AuNPs significantly increased MB singlet oxygen generation, while the efflux pump inhibitor INF-55 further amplified bacterial killing without altering net ROS yield. In vitro assays revealed that INF-55 combined with MB/AuNPs achieved ~59% higher bacterial deactivation compared to MB/AuNPs alone. Molecular docking confirmed stronger binding of INF-55 to the AcrB efflux pump (−9.1 kcal/mol) than MB, supporting its role as a competitive inhibitor that promotes intracellular MB retention. These findings establish a dual-action PDT strategy in which AuNPs enhance ROS production and INF-55 augments antibacterial efficacy via efflux pump inhibition. Together, this platform provides a proof of concept for future translation to biofilm- and tissue-based infection models, and potentially to localized clinical applications such as prosthetic joint, catheter-associated, or chronic wound infections where conventional sterilization or systemic antibiotics are insufficient. Full article

Efficient and localized singlet oxygen (SO) generation is essential for improving antimicrobial photodynamic therapy (aPDT). In this study, a bis-imidazolium-based amphiphilic gelator is used, which self-assembles into a supramolecular gel in a water–ethanol medium and incorporates Rose Bengal (RB) as a photosensitizer. The gel network provides a confined environment that promotes SO formation under light irradiation. RB@Gel was characterized with respect to its morphology, degradation behavior, and swelling properties. Biopharmaceutical assessment included in vitro release, ex vivo permeation studies and Hen’s Egg Test–Chorioallantoic Membrane (HET-CAM) assay. Rheological measurements confirmed a viscoelastic profile, indicating structural stability and suitability for localized therapeutic applications. SO production within the gel was quantified using tetrasodium 9,10-anthracenediyl-bis(methylene)dimalonate (NaABMA), showing higher efficiency than that of RB in solution. The RB@Gel exhibited significant aPDT against E. coli in a direct-surface contact assay. Overall, the RB@Gel provides a stable, suitable platform capable of efficient SO generation and potent antibacterial activity, highlighting its promise for localized aPDT applications. Full article

Hepatocellular carcinoma (HCC) represents the predominant type of primary liver cancer and remains a major global health concern. Current therapeutic strategies—such as surgical resection, radiation, and chemotherapy—provide clinical benefits but are frequently accompanied by considerable adverse effects. Consequently, identifying alternative treatment modalities and developing strategies that allow the use of lower drug doses without compromising therapeutic outcomes are essential goals in HCC management. Among emerging nanoscale platforms, metal–organic frameworks (MOFs) have attracted exceptional interest as promising candidates for targeted drug delivery in cancer therapy. Their inherent characteristics, including highly ordered porosity, large surface area, tunable cavities, adjustable chemical functionality, and remarkable drug-loading capacity, set them apart from conventional porous nanomaterials. Owing to their hierarchical architecture, MOFs are especially suitable for multimodal and synergistic anti-cancer treatments. MOF-based systems have demonstrated the ability to reinforce the performance of several therapeutic modalities, including photodynamic therapy (PDT), photothermal therapy (PTT), chemodynamic therapy (CDT), and sonodynamic therapy (SDT), while also serving as efficient carriers for targeted drug release. Their structural versatility further enables improved drug stability, enhanced solubility, and controlled-release behavior. This review provides an overview of recent progress in MOF-enabled therapeutic strategies and discusses their potential applications in the treatment of HCC. Full article

Accurate tumor visualization remains a central challenge in oncology, as single-modality imaging often lacks the depth, sensitivity, and specificity needed for precise therapeutic guidance. Nano-theranostic platforms address this by combining multimodal imaging with tumor-responsive activation and therapeutic functions within a single system. Advances in carbon-based nanomaterials, metallic and metal oxide nanoplatforms, polymeric and lipid carriers, and biomimetic architectures enable integration of fluorescence (FL), near-infrared II fluorescence (NIR-II FL), photoacoustic (PA), magnetic resonance (MRI), computed tomography (CT), and ultrasound (US) imaging for comprehensive anatomical, functional, and molecular tumor characterization. Coupled with photothermal therapy (PTT), photodynamic therapy (PDT), chemo-dynamic therapy (CDT), ferroptosis induction, metabolic modulation, gas-based therapeutics, and immune activation, these nanoplatforms transform imaging from a passive diagnostic tool into an active, feedback-regulated therapeutic modality. This review outlines the mechanistic foundations, integrated functionalities, and preclinical significance of synergistic imaging-guided nano-theranostics. We also highlight emerging priorities—including adaptive closed-loop platforms, streamlined multifunctional designs, immunotherapy integration, and scalable, biocompatible manufacturing—to advance clinically viable nano-theranostics for precision oncology. Full article

Cancer poses a considerable challenge to global public health and stands as the second leading cause of mortality worldwide. Chemotherapy provides limited benefits for advanced-stage cancer, mainly due to high systemic toxicity and drug resistance. Optimal cancer treatment requires a sophisticated, multidisciplinary collaboration aimed at extending survival, enhancing quality of life, and reducing toxicity. Natural products present advantages, including a wide array of structural diversity, reduced toxicity, improved immune modulation, and the ability to act on multiple targets. Nanomedicine design shows promise in tumor treatment and diagnosis by improving efficacy and minimizing side effects. Due to the heterogeneity of tumors in genetics, metabolism, and microenvironment, natural product-based carrier-free drug delivery platforms have been actively investigated and demonstrated considerable potential for enhanced tumor treatment. “Triadic” strategies can simultaneously perform various functions on a carrier-free intelligent nanoplatform. These include combinational chemotherapy, photodynamic therapy (PDT) with bioimaging and chemotherapy, PDT combined with photothermal therapy (PTT) and chemotherapy, chemo-radio-theranostics, as well as gene therapy (GT) in conjunction with PTT and chemotherapy. This multifaceted approach enhances therapeutic efficacy, reduces multidrug resistance, and minimizes systemic toxicity. This review encompasses recent advancements in cancer therapy using carrier-free “triadic” nanomedicines based on natural products (between 2024 and 2025) and evaluates this evolving field, emphasizing the pivotal role of natural products—berberine, camptothecin, hypericin, erianin, curcumin, lactose, paclitaxel, gambogic acid, and glycyrrhizic acid—in drug delivery platforms. Furthermore, it addresses the challenges and bottlenecks encountered by carrier-free drug delivery platforms, offering valuable insights into their development trajectories. Full article