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Special Issue "Study of Nanoparticles for Photodynamic Therapy and Imaging"

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (15 February 2023) | Viewed by 18415

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Special Issue Editor

Prof. Dr. Victor Loschenov

E-Mail Website1 Website2
Guest Editor

Prokhorov General Physics Institute, Russian Academy of Science, 119991 Moscow, Russia
Interests: photodynamic therapy; fluorescence diagnostics; laser biospectroscopy; nanostructures for biomedicine; fluorescence imaging

Special Issue Information

Dear Colleagues,

Photodynamic therapy has long been applied to cancer and non-cancer treatment owing to the numerous breakthroughs and unique advantages, including invasiveness, the opportunity to control therapy in one session, and real-time regime. However, PDT has several limitations, such as selectivity, phototoxic reactions, subcellular and organelle targeting, etc. Nanotechnology has made a significant contribution to PDT, enabling achievement-targeted methods increasing the selectivity of PDT.

Current challenges in biomedical visualization remain for fast and detailed imaging of tissue microstructures and lesion characterization. Nanotechnology offers the possibility to develop nontoxic contrast agents with a longer circulation time and better visualization quality. Promising to greatly benefit clinical practice, nanoparticle-based contrast agents employed in most common biomedical imaging modalities, addressing their structure-related features, advantages, and limitations are of interest for the present Special Issue.

This issue focuses on the design, synthesis, characterization, and application of nanoparticles of the broad spectrum for photodynamic therapy (PDT), fluorescence diagnosis (FD), and imaging. A better understanding of novel concepts in these fields will be useful for improving photodynamic effectiveness and imaging strategies and limiting side effects to normal tissues. We believe that continuous advances in the use of nanomaterials will enhance future development in the treatment and diagnosis of oncological and other diseases.

I hope you will join us and contribute to the success of this Special Issue by submitting the latest and unique results of your research in this interesting field.

Prof. Dr. Victor Loschenov
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

nanoparticle
photodynamic therapy
fluorescence diagnosis
biomedical imaging
drug delivery
targeting
modeling
theranostic

Published Papers (11 papers)

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Research

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Open AccessArticle

Mesenchymal Stem Cell Membrane-Coated TPCS_2a-Loaded Nanoparticles for Breast Cancer Photodynamic Therapy

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Pharmaceutics 2023, 15(6), 1654; https://doi.org/10.3390/pharmaceutics15061654 - 04 Jun 2023

Viewed by 1284

Abstract

Despite substantial improvements in breast cancer (BC) treatment there is still an urgent need to find alternative treatment options to improve the outcomes for patients with advanced-stage disease. Photodynamic therapy (PDT) is gaining a lot of attention as a BC therapeutic option because of its selectivity and low off-target effects. However, the hydrophobicity of photosensitizers (PSs) impairs their solubility and limits the circulation in the bloodstream, thus representing a major challenge. The use of polymeric nanoparticles (NPs) to encapsulate the PS may represent a valuable strategy to overcome these issues. Herein, we developed a novel biomimetic PDT nanoplatform (NPs) based on a polymeric core of poly(lactic-co-glycolic)acid (PLGA) loaded with the PS meso-tetraphenylchlorin disulfonate (TPCS_2a). TPCS_2a@NPs of 98.89 ± 18.56 nm with an encapsulation efficiency percentage (EE%) of 81.9 ± 7.92% were obtained and coated with mesenchymal stem cells-derived plasma membranes (mMSCs) (mMSC-TPCS_2a@NPs, size of 139.31 ± 12.94 nm). The mMSC coating armed NPs with biomimetic features to impart long circulation times and tumor-homing capabilities. In vitro, biomimetic mMSC-TPCS_2a@NPs showed a decrease in macrophage uptake of 54% to 70%, depending on the conditions applied, as compared to uncoated TPCS_2a@NPs. Both NP formulations efficiently accumulated in MCF7 and MDA-MB-231 BC cells, while the uptake was significantly lower in normal breast epithelial MCF10A cells with respect to tumor cells. Moreover, encapsulation of TPCS_2a in mMSC-TPCS_2a@NPs effectively prevents its aggregation, ensuring efficient singlet oxygen (¹O₂) production after red light irradiation, which resulted in a considerable in vitro anticancer effect in both BC cell monolayers (IC₅₀ < 0.15 µM) and three-dimensional spheroids. Full article

(This article belongs to the Special Issue Study of Nanoparticles for Photodynamic Therapy and Imaging)

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Open AccessArticle

Autophagy Regulation Using Multimodal Chlorin e6-Loaded Polysilsesquioxane Nanoparticles to Improve Photodynamic Therapy

Hemapriyadarshini Vadarevu

Adeola Julian Sorinolu

Mariya Munir

and

Juan L. Vivero-Escoto

Pharmaceutics 2023, 15(5), 1548; https://doi.org/10.3390/pharmaceutics15051548 - 20 May 2023

Cited by 1 | Viewed by 860

Abstract

Photodynamic therapy (PDT) is a promising anticancer noninvasive technique that relies on the generation of reactive oxygen species (ROS). Unfortunately, PDT still has many limitations, including the resistance developed by cancer cells to the cytotoxic effect of ROS. Autophagy, which is a stress response mechanism, has been reported as a cellular pathway that reduces cell death following PDT. Recent studies have demonstrated that PDT in combination with other therapies can eliminate anticancer resistance. However, combination therapy is usually challenged by the differences in the pharmacokinetics of the drugs. Nanomaterials are excellent delivery systems for the efficient codelivery of two or more therapeutic agents. In this work, we report on the use of polysilsesquioxane (PSilQ) nanoparticles for the codelivery of chlorin-e6 (Ce6) and an autophagy inhibitor for early- or late-stage autophagy. Our results, obtained from a reactive oxygen species (ROS) generation assay and apoptosis and autophagy flux analyses, demonstrate that the reduced autophagy flux mediated by the combination approach afforded an increase in the phototherapeutic efficacy of Ce6-PSilQ nanoparticles. We envision that the promising results in the use of multimodal Ce6-PSilQ material as a codelivery system against cancer pave the way for its future application with other clinically relevant combinations. Full article

(This article belongs to the Special Issue Study of Nanoparticles for Photodynamic Therapy and Imaging)

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Open AccessArticle

Lipid Liquid Crystal Nanoparticles: Promising Photosensitizer Carriers for the Treatment of Infected Cutaneous Wounds

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Pharmaceutics 2023, 15(2), 305; https://doi.org/10.3390/pharmaceutics15020305 - 17 Jan 2023

Cited by 1 | Viewed by 1430

Abstract

Cutaneous chronic wounds impose a silent pandemic that affects the lives of millions worldwide. The delayed healing process is usually complicated by opportunistic bacteria that infect wounds. Staphylococcus aureus is one of the most prevalent bacteria in infected cutaneous wounds, with the ability to form antibiotic-resistant biofilms. Recently, we have demonstrated the potential of gallium protoporphyrin lipid liquid crystalline nanoparticles (GaPP-LCNP) as a photosensitizer against S. aureus biofilms in vitro. Herein, we investigate the potential of GaPP-LCNP using a pre-clinical model of infected cutaneous wounds. GaPP-LCNP showed superior antibacterial activity compared to unformulated GaPP, reducing biofilm bacterial viability by 5.5 log₁₀ compared to 2.5 log₁₀ in an ex vivo model, and reducing bacterial viability by 1 log₁₀ in vivo, while unformulated GaPP failed to reduce bacterial burden. Furthermore, GaPP-LCNP significantly promoted wound healing through reduction in the bacterial burden and improved early collagen deposition. These findings pave the way for future pre-clinical investigation and treatment optimizations to translate GaPP-LCNP towards clinical application. Full article

(This article belongs to the Special Issue Study of Nanoparticles for Photodynamic Therapy and Imaging)

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Graphical abstract

Open AccessArticle

Influence of Hydrophobic Side-Chain Length in Amphiphilic Gradient Copoly(2-oxazoline)s on the Therapeutics Loading, Stability, Cellular Uptake and Pharmacokinetics of Nano-Formulation with Curcumin

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Pharmaceutics 2022, 14(12), 2576; https://doi.org/10.3390/pharmaceutics14122576 - 23 Nov 2022

Cited by 1 | Viewed by 1133

Abstract

Due to the simple one-step preparation method and a promising application in biomedical research, amphiphilic gradient copoly(2-oxazoline)s are gaining more and more interest compared to their analogous block copolymers. In this work, the curcumin solubilization ability was tested for a series of amphiphilic gradient copoly(2-oxazoline)s with different lengths of hydrophobic side-chains, consisting of 2-ethyl-2-oxazoline as a hydrophilic monomer and 2-(4-alkyloxyphenyl)-2-oxazoline as a hydrophobic monomer. It is shown that the length of the hydrophobic side-chain in the copolymers plays a crucial role in the loading of curcumin onto the self-assembled nanoparticles. The kinetic stability of self-assembled nanoparticles studied using FRET shows a link between their integrity and cellular uptake in human glioblastoma cells. The present study demonstrates how minor changes in the molecular structure of gradient copoly(2-oxazoline)s can lead to significant differences in the loading, stability, cytotoxicity, cellular uptake, and pharmacokinetics of nano-formulations containing curcumin. The obtained results on the behavior of the complex of gradient copoly(2-oxazoline)s and curcumin may contribute to the development of effective next-generation polymeric nanostructures for biomedical applications. Full article

(This article belongs to the Special Issue Study of Nanoparticles for Photodynamic Therapy and Imaging)

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Open AccessArticle

Novel Scintillating Nanoparticles for Potential Application in Photodynamic Cancer Therapy

Bianca A. da Silva

Michael Nazarkovsky

Helmut Isaac Padilla-Chavarría

Edith Alejandra C. Mendivelso

Heber L. de Mello

Cauê de S. C. Nogueira

Rafael dos S. Carvalho

Marco Cremona

Volodymyr Zaitsev

Yutao Xing

Rodrigo da C. Bisaggio

Luiz A. Alves

and

Jiang Kai

Pharmaceutics 2022, 14(11), 2258; https://doi.org/10.3390/pharmaceutics14112258 - 22 Oct 2022

Cited by 2 | Viewed by 1160

Abstract

The development of X-ray-absorbing scintillating nanoparticles is of high interest for solving the short penetration depth problem of visible and infrared light in photodynamic therapy (PDT). Thus, these nanoparticles are considered a promising treatment for several types of cancer. Herein, gadolinium oxide nanoparticles doped with europium ions (Gd₂O₃:Eu³⁺) were obtained by using polyvinyl alcohol as a capping agent. Hybrid silica nanoparticles decorated with europium-doped gadolinium oxide (SiO₂-Gd₂O₃:Eu³⁺) were also prepared through the impregnation method. The synthesized nanoparticles were structurally characterized and tested to analyze their biocompatibility. X-ray diffraction, scanning electron microscopy, and transmission electron microscopy confirmed the high crystallinity and purity of the Gd₂O₃:Eu³⁺ particles and the homogeneous distribution of nanostructured rare earth oxides throughout the fumed silica matrix for SiO₂-Gd₂O₃:Eu³⁺. Both nanoparticles displayed stable negative ζ-potentials. The photoluminescence properties of the materials were obtained using a Xe lamp as an excitation source, and they exhibited characteristic Eu³⁺ bands, including at 610 nm, which is the most intense transition band of this ion. Cytotoxicity studies on mouse glioblastoma GL261 cells indicated that these materials appear to be nontoxic from 10 to 500 μg·mL⁻¹ and show a small reduction in viability in non-tumor cell lines. All these findings demonstrate their possible use as alternative materials in PDT. Full article

(This article belongs to the Special Issue Study of Nanoparticles for Photodynamic Therapy and Imaging)

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Open AccessArticle

Conjugation of Hypericin to Gold Nanoparticles for Enhancement of Photodynamic Therapy in MCF-7 Breast Cancer Cells

Dimakatso Mokoena

Blassan P. George

and

Heidi Abrahamse

Pharmaceutics 2022, 14(10), 2212; https://doi.org/10.3390/pharmaceutics14102212 - 18 Oct 2022

Cited by 3 | Viewed by 1246

Abstract

Breast cancer, among the different types of cancer, is one of the most diagnosed cancers and the leading cause of mortalities amongst women. Factors, including genetic and epigenetic alterations in tumors, make it resistant to therapies, which results in treatment failures and/or recurrence. Furthermore, the existing therapies have many unfavorable side effects leading to poor prognosis and reduced therapeutic outcomes. Photodynamic therapy (PDT) is one of the most effective cancer therapies with increased selectivity and specificity toward cancer cells. As a result, the use of gold nanoparticles (AuNP) further improves the effectiveness of PDT by increasing the drug loading capacity into the cells. In this study, hypericin (Hyp) photosensitizer (PS) was adsorbed on gold nanoparticles (AuNPs) by sonication to achieve physical adsorption of the PS to AuNP. The resulting compound was characterized by FTIR, Zeta potential, UV-Vis spectroscopy, and TEM. The compound was used for the PDT treatment of MCF-7 human breast cancer in vitro. Cellular responses at 12 h post-PDT at 10 J/cm² were observed. Cellular morphology, LDH membrane integrity, ATP luminescence assay, and Annexin V/PI staining were performed. The results demonstrated typical cell death morphological features while the biochemical responses indicated increased LDH and decreased ATP levels. In conclusion, this study presents an insight into the application of advanced PDT in breast cancer cells by inducing cancer cell death in vitro via apoptosis. Full article

(This article belongs to the Special Issue Study of Nanoparticles for Photodynamic Therapy and Imaging)

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Open AccessArticle

Theranostic Properties of Crystalline Aluminum Phthalocyanine Nanoparticles as a Photosensitizer

Vladimir I. Makarov

Daria V. Pominova

Anastasiya V. Ryabova

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Pharmaceutics 2022, 14(10), 2122; https://doi.org/10.3390/pharmaceutics14102122 - 06 Oct 2022

Cited by 2 | Viewed by 1007

Abstract

The study of phthalocyanines, known photosensitizers, for biomedical applications has been of high research interest for several decades. Of specific interest, nanophotosensitizers are crystalline aluminum phthalocyanine nanoparticles (AlPc NPs). In crystalline form, they are water-insoluble and atoxic, but upon contact with tumors, immune cells, or pathogenic microflora, they change their spectroscopic properties (acquire the ability to fluoresce and become phototoxic), which makes them upcoming agents for selective phototheranostics. Aqueous colloids of crystalline AlPc NPs with a hydrodynamic size of 104 ± 54 nm were obtained using ultrasonic dispersal and centrifugation. Intracellular accumulation and localization of AlPc were studied on HeLa and THP-1 cell cultures and macrophages (M0, M1, M2) by fluorescence microscopy. Crystallinity was assessed by XRD spectroscopy. Time-resolved spectroscopy was used to obtain characteristic fluorescence kinetics of AlPc NPs upon interaction with cell cultures. The photodynamic efficiency and fluorescence quantum yield of AlPc NPs in HeLa and THP-1 cells were evaluated. After entering the cells, AlPc NPs localized in lysosomes and fluorescence corresponding to individual AlPc molecules were observed, as well as destruction of lysosomes and a rapid decrease in fluorescence intensity during photodynamic action. The photodynamic efficiency of AlPc NPs in THP-1 cells was almost 1.8-fold that of the molecular form of AlPc (Photosens). A new mechanism for the occurrence of fluorescence and phototoxicity of AlPc NPs in interaction with cells is proposed. Full article

(This article belongs to the Special Issue Study of Nanoparticles for Photodynamic Therapy and Imaging)

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Open AccessArticle

Association of Indocyanine Green with Chitosan Oleate Coated PLGA Nanoparticles for Photodynamic Therapy

and

Maria Cristina Bonferoni

Pharmaceutics 2022, 14(8), 1740; https://doi.org/10.3390/pharmaceutics14081740 - 20 Aug 2022

Cited by 3 | Viewed by 1332

Abstract

Indocyanine green (ICG) is a safe dye widely used in the biomedical field. Its photodynamic effect (PDT), originating from laser irradiation at 803 nm, opens interesting perspectives in theranostic applications. To overcome its low water stability, ICG can be shielded with nanoparticles (NPs). In this work, previously developed NPs based on poly lactic-co-glycolic acid (PLGA) coated with chitosan oleate (CS-OA) and loaded with resveratrol as a hydrophobic model drug have been proposed as an ICG carrier. These systems have been selected for their observed immunostimulatory properties. The possible loading of the dye by adsorption onto NP surface by electrostatic interaction was studied here in comparison with the encapsulation into the PLGA core. The ICG-chitosan (CS) interaction has been characterized by spectrophotometry, spectroscopy and in-cell in vitro assays. Fluorescence quenching was observed due to the ionic interaction between ICG and CS and was studied considering the dye:polymer stoichiometry and the effect of the NP dilution in cell culture medium (DMEM). The NP systems have been compared in vitro, assessing their behaviour in Caco-2 cell lines. A reduction in cell viability was observed after irradiation of ICG associated with NPs, evident also for the samples loaded by adsorption. These findings open the opportunity to exploit the association of PDT’s effect on ICG with the properties of CS-OA coated NPs, whose immunostimulatory effect can be associated with PDT mechanism in cancer therapy. Full article

(This article belongs to the Special Issue Study of Nanoparticles for Photodynamic Therapy and Imaging)

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Review

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Open AccessReview

Nanotechnology in Cancer Diagnosis and Treatment

Noor Alrushaid

Firdos Alam Khan

Ebtesam Abdullah Al-Suhaimi

and

Abdelhamid Elaissari

Pharmaceutics 2023, 15(3), 1025; https://doi.org/10.3390/pharmaceutics15031025 - 22 Mar 2023

Cited by 2 | Viewed by 4236

Abstract

Traditional cancer diagnosis has been aided by the application of nanoparticles (NPs), which have made the process easier and faster. NPs possess exceptional properties such as a larger surface area, higher volume proportion, and better targeting capabilities. Additionally, their low toxic effect on healthy cells enhances their bioavailability and t-half by allowing them to functionally penetrate the fenestration of epithelium and tissues. These particles have attracted attention in multidisciplinary areas, making them the most promising materials in many biomedical applications, especially in the treatment and diagnosis of various diseases. Today, many drugs are presented or coated with nanoparticles for the direct targeting of tumors or diseased organs without harming normal tissues/cells. Many types of nanoparticles, such as metallic, magnetic, polymeric, metal oxide, quantum dots, graphene, fullerene, liposomes, carbon nanotubes, and dendrimers, have potential applications in cancer treatment and diagnosis. In many studies, nanoparticles have been reported to show intrinsic anticancer activity due to their antioxidant action and cause an inhibitory effect on the growth of tumors. Moreover, nanoparticles can facilitate the controlled release of drugs and increase drug release efficiency with fewer side effects. Nanomaterials such as microbubbles are used as molecular imaging agents for ultrasound imaging. This review discusses the various types of nanoparticles that are commonly used in cancer diagnosis and treatment. Full article

(This article belongs to the Special Issue Study of Nanoparticles for Photodynamic Therapy and Imaging)

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Open AccessReview

Nontoxic Fluorescent Nanoprobes for Multiplexed Detection and 3D Imaging of Tumor Markers in Breast Cancer

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Pharmaceutics 2023, 15(3), 946; https://doi.org/10.3390/pharmaceutics15030946 - 15 Mar 2023

Viewed by 1393

Abstract

Multiplexed fluorescent immunohistochemical analysis of breast cancer (BC) markers and high-resolution 3D immunofluorescence imaging of the tumor and its microenvironment not only facilitate making the disease prognosis and selecting effective anticancer therapy (including photodynamic therapy), but also provides information on signaling and metabolic mechanisms of carcinogenesis and helps in the search for new therapeutic targets and drugs. The characteristics of imaging nanoprobe efficiency, such as sensitivity, target affinity, depth of tissue penetration, and photostability, are determined by the properties of their components, fluorophores and capture molecules, and by the method of their conjugation. Regarding individual nanoprobe components, fluorescent nanocrystals (NCs) are widely used for optical imaging in vitro and in vivo, and single-domain antibodies (sdAbs) are well established as highly specific capture molecules in diagnostic and therapeutic applications. Moreover, the technologies of obtaining functionally active sdAb–NC conjugates with the highest possible avidity, with all sdAb molecules bound to the NC in a strictly oriented manner, provide 3D-imaging nanoprobes with strong comparative advantages. This review is aimed at highlighting the importance of an integrated approach to BC diagnosis, including the detection of biomarkers of the tumor and its microenvironment, as well as the need for their quantitative profiling and imaging of their mutual location, using advanced approaches to 3D detection in thick tissue sections. The existing approaches to 3D imaging of tumors and their microenvironment using fluorescent NCs are described, and the main comparative advantages and disadvantages of nontoxic fluorescent sdAb–NC conjugates as nanoprobes for multiplexed detection and 3D imaging of BC markers are discussed. Full article

(This article belongs to the Special Issue Study of Nanoparticles for Photodynamic Therapy and Imaging)

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Open AccessReview

Quantum Dots Mediated Imaging and Phototherapy in Cancer Spheroid Models: State of the Art and Perspectives

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Pharmaceutics 2022, 14(10), 2136; https://doi.org/10.3390/pharmaceutics14102136 - 08 Oct 2022

Cited by 6 | Viewed by 1861

Abstract

Quantum Dots (QDs) are fluorescent nanoparticles known for their exceptional optical properties, i.e., high fluorescence emission, photostability, narrow emission spectrum, and broad excitation wavelength. These properties make QDs an exciting choice for bioimaging applications, notably in cancer imaging. Challenges lie in their ability to specifically label targeted cells. Numerous studies have been carried out with QDs coupled to various ligands like peptides, antibodies, aptamers, etc., to achieve efficient targeting. Most studies were conducted in vitro with two-dimensional cell monolayers (n = 8902) before evolving towards more sophisticated models. Three-dimensional multicellular tumor models better recapitulate in vivo conditions by mimicking cell-to-cell and cell-matrix interactions. To date, only few studies (n = 34) were conducted in 3D in vitro models such as spheroids, whereas these models could better represent QDs behavior in tumors compared to monolayers. Thus, the purpose of this review is to present a state of the art on the studies conducted with Quantum Dots on spheroid models for imaging and phototherapy purposes. Full article

(This article belongs to the Special Issue Study of Nanoparticles for Photodynamic Therapy and Imaging)

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