Photosensitizer Release Research Articles

Photocytotoxic and cellular metabolism studies of curcuminoid-BF2 nanoaggregates in human carcinoma cells

Heavy atom-free photosensitizers represent a paradigm shift in the field of photodynamic therapy (PDT), offering a safer and more versatile alternative to traditional photosensitizers. As research progresses, the development of novel heavy-atom free compounds holds the potential to enhance the effectiveness and broaden the application of PDT, enabling the way for more targeted and less toxic cancer treatments. In this article, we report the application of heavy atom free curcuminoid BF2 (Diethylamine-CUR-BF2) containing acid sensitive amine group. Diethylamine-CUR-BF2 absorbs in deep red region at ∼618 nm and has high molar absorption coefficient. Nanoaggregates of Diethylamine-CUR-BF2 dispersed in aqueous medium showed high singlet oxygen production efficiency. The release kinetics of Diethylamine-CUR-BF2 showed efficient release of photosensitizer in slight acidic medium (at pH=5.0). Further, applications of Diethylamine-CUR-BF2 nanoaggregates in photocytotoxic studies using MCF-7 and A549 cells showed IC50 values 5.15 ± 1.4 μM and 8.05 ± 0.4 μM respectively. Cell death mechanism explored for photocytotoxicity studies utilizing Diethylamine-CUR-BF2 nanoaggregates is found to be apoptosis which is considered as normal programmed cell death pathway. Additionally, NADH FLIM studies revealed that the compound had an impact on cellular metabolism, prompting a shift from OXPHOS to glycolysis.

Synthesis and applications of metal organic frameworks in photodynamic therapy

Metal organic frameworks (MOFs) consist of metal atoms or clusters, coordinated to organic ligands to form macromolecular super structures, with pores large enough to host free drug molecules, including photodynamic therapy (PDT) photosensitizers. This review presents examples of applications in PDT of various types of MOFs. To contextualize the discussions of their PDT applications, general procedures of MOF synthesis are considered. Applications of MOFs in PDT are described using examples of several combination therapy innovations developed for the purpose of solving some of the key challenges in the clinical translation value chain of PDT. The review presents evidence to show that the explosion of research in MOFs is due to their capability for applications as carriers and delivery systems for PDT photosensitizers. It also shows their unique applications as platforms for combination therapies, for stimulus responsive release of photosensitizer and drug molecules, for cancer cell targeting, and for auxiliary enhancement of efficacy. Published literature on MOFs has been on the rise since the eighties. In Scopus, the applications of MOFs in PDT increased from 1 article in 2010, to 169 articles in 2023, whereas published literature on MOFs generally, increased from 878 to 11644 during this period. Research on the applications of MOFs in PDT has therefore increased more than that of MOFs generally. Literature on the applications of MOFs in PDT increased by between 0.7% to 1.45% relative to published literature on MOFs generally. Clearly, MOFs are researched to overcome challenges of and improve PDT efficacy, more than they are generally.

Supramolecular Switch for the Regulation of Antibacterial Efficacy of Near-Infrared Photosensitizer.

The global antibiotic resistance crisis has drawn attention to the development of treatment methods less prone to inducing drug resistance, such as antimicrobial photodynamic therapy (aPDT). However, there is an increasing demand for new photosensitizers capable of efficiently absorbing in the near-infrared (NIR) region, enabling antibacterial treatment in deeper sites. Additionally, advanced strategies need to be developed to avert drug resistance stemming from prolonged exposure. Herein, we have designed a conjugated oligoelectrolyte, namely TTQAd, with a donor-acceptor-donor (D-A-D) backbone, enabling the generation of reactive oxygen species (ROS) under NIR light irradiation, and cationic adamantaneammonium groups on the side chains, enabling the host-guest interaction with curcubit[7]uril (CB7). Due to the amphiphilic nature of TTQAd, it could spontaneously form nanoassemblies in aqueous solution. Upon CB7 treatment, the positive charge of the cationic adamantaneammonium group was largely shielded by CB7, leading to a further aggregation of the nanoassemblies and a reduced antibacterial efficacy of TTQAd. Subsequent treatment with competitor guests enables the release of TTQAd and restores its antibacterial effect. The reversible supramolecular switch for regulating the antibacterial effect offers the potential for the controlled release of active photosensitizers, thereby showing promise in preventing the emergence of drug-resistant bacteria.

Dual-Responsive hollow mesoporous organosilicon nanocarriers for photodynamic therapy

Hypothesis: The nano-delivery platform, -SS-HMONs@MB@MnO2 nanoparticles (SMM NPs) loaded with methylene blue (MB) as photosensitizer have excellent photodynamic therapy (PDT) effect. The disulfide bond and MnO2 give the shell redox-responsive properties. SMM NPs consume glutathione (GSH) in tumor cells, reducing the scavenging of reactive oxygen species (ROS) by GSH and enhancing the PDT effect of MB.Experiments: The GSH dual-responsive nano-delivery platform, was designed and constructed by using disulfide-doped hollow mesoporous organosilicon nanoparticles (-SS-HMONs) as intermediate responsive layer, loaded with MB as photosensitizer and coated with MnO2 as shells. The MB photosensitizer release and GSH response were characterized. The PDT effect of nanoparticles was evaluated.Findings: The SMM NPs were uniform in size and well dispersed. The nanoparticles could react with GSH, leading to the decomposition of MnO2 shells and the breakage of disulfide bonds in -SS-HMONs, resulted in the release of MB photosensitizer. The cell experiment showed that SMM NPs had good ROS generating ability and PDT effect after being sucked by tumor cells, which could effectively kill tumor cells. However, in vivo experiments demonstrated that SMM NPs showed slight inhibition on tumor growth. The actual effect in animals was different from the effect in cells.

Hypoxia and Singlet Oxygen Dual-Responsive Micelles for Photodynamic and Chemotherapy Therapy Featured with Enhanced Cellular Uptake and Triggered Cargo Delivery.

Combination therapy provides better outcomes than a single therapy and becomes an efficient strategy for cancer treatment. In this study, we designed a hypoxia- and singlet oxygen-responsive polymeric micelles which contain azo and nitroimidazole groups for enhanced cellular uptake, repaid cargo release, and codelivery of photosensitizer Ce6 and hypoxia-activated prodrug tirapazamine TPZ (DHM-Ce6@TPZ), which could be used for combining Ce6-mediated photodynamic therapy (PDT) and PDT-activated chemotherapy to enhance the therapy effect of cancer. The hypoxia- and singlet oxygen-responsive polymeric micelles DHM-Ce6@TPZ were prepared by film hydration method. The morphology, physicochemical properties, stimuli responsiveness, in vitro singlet oxygen production, cellular uptake, and cell viability were evaluated. In addition, the in vivo therapeutic effects of the micelles were verified using a tumor xenograft mice model. The resulting dual-responsive micelles not only increased the concentration of intracellular photosensitizer and TPZ, but also facilitated photosensitizer and TPZ release for enhanced integration of photodynamic and chemotherapy therapy. As a photosensitizer, Ce6 induced PDT by generating toxic singlet reactive oxygen species (ROS), resulting in a hypoxic tumor environment to activate the prodrug TPZ to achieve efficient chemotherapy, thereby evoking a synergistic photodynamic and chemotherapy therapeutic effect. The cascade synergistic therapeutic effect of DHM-Ce6@TPZ was effectively evaluated both in vitro and in vivo to inhibit tumor growth in a breast cancer mice model. The designed multifunctional micellar nano platform could be a convenient and powerful vehicle for the efficient co-delivery of photosensitizers and chemical drugs for enhanced synergistic photodynamic and chemotherapy therapeutic effect of cancer.

Enzyme-mediated fabrication of nanocomposite hydrogel microneedles for tunable mechanical strength and controllable transdermal efficiency

Microneedles (MNs) are increasingly used in transdermal drug delivery due to high bioavailability, simple operation, and improved patient compliance. However, further clinical applications are hindered by unsatisfactory mechanical strength and uncontrolled drug release. Herein, an enzyme-mediated approach is reported for the fabrication of nanocomposite hydrogel-based MNs with tunable mechanical strength and controllable transdermal efficiency. As a proof-of-concept, tetrakis(1-methyl-4-pyridinio)porphyrin (TMPyP) was chosen as a model drug for photodynamic therapy of melanoma. TMPyP-loaded PLGA nanoparticles (NP/TMPyP) served as an inner phase of MNs for controlled release of photosensitizers, and enzyme-mediated hyaluronic acid-tyramine (HAT) hydrogels served as an external phase for optimizing the mechanical strength of MNs. By changing the concentration of HRP and H2O2, three types of MNs were fabricated for transdermal delivery of TMPyP, which demonstrated different cross-linking densities and various mechanical strength. Among the three MNs, the HAT-Medium@NP/TMPyP-MN with a medium mechanical strength exhibited the highest values of transdermal efficiency in vitro and the longest retention time in vivo. As compared to pure TMPyP and TMPyP-loaded nanoparticles, the HAT-Medium@NP/TMPyP-MN demonstrated higher anticancer efficacy in both melanoma A375 cells and a xenografted tumor mouse model. Therefore, the enzyme-mediated nanocomposite hydrogel MNs show great promise in the transdermal delivery of therapeutic drugs with enhanced performance. Statement of SignificanceThis study reports an enzyme-mediated approach for the fabrication of photodynamically-active microneedles (HAT@NP/TMPyP-MNs) with tunable mechanical strength and controllable transdermal efficiency. On one hand, HAT hydrogels that bear different cross-linking densities, facilitate tunable mechanical strength and optimized transdermal performances of MNs; on the other hand, NP/TMPyP and HAT network contribute to sustained release of photosensitizers. Comparing to other formulation (i.e., NP/TMPyP or TMPyP), the HAT-Medium@NP/TMPyP-MN exhibited excelling anticancer efficacy in photodynamic therapy in vitro and in vivo. We believe that the combination of enzyme-mediated polymeric cross-linking and slow-releasing nano-vehicles in a single nanocomposite platform provides a versatile approach for the fabrication of MNs with enhanced therapeutic efficacy, which holds great promise in the transdermal delivery of various therapeutic drugs in future.

Mitochondria-targeted NO donor enables synergistic NO and photodynamic therapies for effective inhibition of cancer cell proliferation and migration

Previously reported light-controlled nitric oxide donors are usually activated by blue or green light. The insufficient ability of short wavelength light to penetrate tissues and its potential phototoxicity to living organisms greatly restricted in vivo applications. This study presents the development of a novel mitochondria-targeted nitric oxide donor, R–NO, capable of controlled nitric oxide and photosensitizer release under white light irradiation in mitochondria. R–NO is capable of generating nitric oxide and R–NH, a novel photosensitizer that can produce O2•- upon irradiation with a single light source. In addition, the highly toxic ONOO− can be produced by the rapid reaction of nitric oxide and O2•-. Harnessing the synergistic effects of PDT, nitric oxide therapy and highly toxic ONOO−, the proliferation and migration of cancer cells can be significantly inhibited upon light irradiation with R–NO. Futhermore, our MTT experiments demonstrated that simultaneous producing of O2•- and nitric oxide in the same region is crucial for efficient cancer cell inhibition. These interesting findings underscore the enhanced synergistic effect achieved by combining PDT and NO therapy in a single molecule for cancer cell treatment.

Light-responsive smart nanocarriers for wirelessly controlled photodynamic therapy for prostate cancers.

Photodynamic therapy (PDT) is an effective non-invasive or minimally invasive treatment method against different tumors. Loading photosensitizers in nanocarriers can potentially increase their accumulation in tumor sites. However, the PDT efficacy may be hindered because of self-quenching of the encapsulated photosensitizer and the small diffusion radii of the generated reactive oxygen species (ROS). Herein, light responsive nano assemblies composed of (Polyethylene glycol)-block-poly(4,5-dimethoxy-2-nitrobenzylmethacrylate) (PEG-b-PNBMA) were designed and loaded with the photosensitizer, Rose Bengal lactone (RB), to act as a smart nanocarrier (RB-M) for the delivery of the photosensitizer. A wirelessly activated light-emitting diode (LED) implant was designed to programmatically induce the release of the loaded RB and activate PDT after diffusion of RB into the cytoplasm. The results showed that sequential '405-580 nm' irradiation of the RB-M treated 22RV1 cells resulted in the highest PDT outcome among different irradiation protocols. The combination of this smart nanocarrier and sequential '405-580 nm' irradiation strategy exhibited good PDT efficacy against 2D 22RV1 prostate cancer cells as well as 3D cancer cell spheroids. This platform overcome the light penetration limitations in PDT, and can potentially be applied in cancer bearing patients who are unfit for chemotherapy. STATEMENT OF SIGNIFICANCE: Nanocarriers for the delivery of photosensitizer in photodynamic therapy may result in relatively low therapeutic efficacy because of self-quenching of the encapsulated photosensitizer and the small diffusion radii of the generated reactive oxygen species (ROS). Light responsive smart nanocarriers can potentially overcome this challenge. In this study, a light responsive polymer (Polyethylene glycol)-block-poly(4,5-dimethoxy-2-nitrobenzylmethacrylate) (PEG-b-PNBMA) was synthesized and utilized to fabricate the smart nanocarrier. A wirelessly activated light-emitting diode (LED) implant was designed for light delivery in deep tissue. This new approach permits wirelessly and programmatically control of photosensitizer release and PDT activation under deep tissue, thus significantly enhancing PDT efficacy against prostate cancer cells as well as 3D cancer cell spheroids. This design should have a significant impact on controllable PDT under deep tissue.

Metal-Organic Framework for Hypoxia/ROS/pH Triple-Responsive Cargo Release.

Nanoparticulate antitumor photodynamic therapy (PDT) is suffering from a very short lifetime, limited diffusion distance of reactive oxygen species (ROS). Herein, a hypoxia/ROS/pH triple-responsive metal-organic framework (MOF) is designed to facilitate the on-demand release of photosensitizers and hence enhanced PDT efficacy. Tailored azo-containing imidazole ligand is coordinated with zinc to form MOF where photosensitizer (Chlorin e6/Ce6) is encapsulated. Azo can be reduced by overexpressed azoreductase in hypoxic tumor cells, resulting in depletion of glutathione (GSH) and thioredoxin (Trx) which are major antioxidants against ROS oxidative damage in PDT, resulting in rapid cargo release and additional efficacy amplification. The imidazole ionization causes a proton sponge effect to ensure the disintegration of the nanocarriers in acidic organelles, allowing the rapid release of Ce6 through lysosome escape. Under light irradiation, ROS produced by Ce6 may oxidize imidazole to urea, resulting in rapid cargo release. All of the triggers are expected to show interactive synergism. The pH- and hypoxia-responsiveness can improve the release rate of Ce6 for enhanced PDT therapy, whereas the consumption of oxygen by PDT may induce elevated hypoxia and hence in turn enhanced cargo release. This work highlights the role of triple-responsive nanocarriers for triggered photosensitizer release and improved antitumor PDT efficacy.

EPS9.08 Antimicrobial photodynamic therapy with Ru(II)-loaded polymer nanocarriers towards treatment of bacterial lung infections: Proof-of-concept using cystic fibrosis Pseudomonas aeruginosa isolates

Objectives: Cystic fibrosis (CF) patients suffer from severe chronic lung infections that are caused mainly by Pseudomonas aeruginosa. As this highly adaptable pathogen is increasingly resistant to antibiotics, the development of new antimicrobial treatments is of major interest. Antimicrobial photodynamic therapy (aPDT) combines the use of photosensitizers (PS) and light to locally generate reactive oxygen species, including singlet oxygen (1O2), at the infection site. In this work, ruthenium (II) PS complexes were incorporated into polymeric micelles and vesicles to overcome the limited solubility and stability of the neat complexes, and to facilitate their delivery through the highly viscous airway mucus. Further, on-demand bacterial enzyme-triggered release of PS should minimize lung tissue damage, while maximizing local bacterial killing efficiency.

Activatable Graphene Quantum-Dot-Based Nanotransformers for Long-Period Tumor Imaging and Repeated Photodynamic Therapy.

Photodynamic therapy (PDT) is considered as an emerging therapeutic modality against cancer with high spatiotemporal selectivity because the utilized photosensitizers (PSs) are only active and toxic upon light irradiation. To maximize its effectiveness, PDT is usually applied repetitively for ablating various tumors. However, the total overdose of PSs from repeated administrations causes severe side effects. Herein, acidity-activated graphene quantum dots-based nanotransformers (GQD NT) are developed as PS vehicles for long-period tumor imaging and repeated PDT. Under the guidance of Arg-Gly-Asp peptide, GQD NT targets to tumor tissues actively, and then loosens and enlarges in tumor acidity, thus promising long tumor retention. Afterwards, GQD NT transforms into small pieces for better penetration in tumor. Upon laser irradiation, GQD NT generates mild hyperthermia that enhances cell membrane permeability and further promotes the PSs uptake. Most intriguingly, the as-prepared GQD NT not only "turns-on" fluorescence/magnetic resonance signals, but also achieves efficient repeated PDT. Notably, the total PSs dose is reduced to 3.5µmolkg-1 , which is 10-30times lower than that of other reported works. Overall, this study exploits a smart vehicle to enhance accumulation, retention, and release of PSs in tumors through programmed deformation, thus overcoming the overdose obstacle in repeated PDT.

Dual irradiation-triggered anticancer therapeutics composed of polydopamine-coated gold nanoparticles.

The therapeutic efficacy of nanoparticles depends on their ability to release encapsulated photosensitizers. Here, surface-engineered metallic gold nanoparticles (AuNP) were irradiated with dual near-infrared (NIR) light to enhance the release of photosensitizer. Dopamine hydrochloride was surface-polymerized to polydopamine (PDA) layers on AuNP, and chlorin-e6 (Ce6) was chemically tethered to primary amines of PDA. The resulting Ce6-conjugated AuNP were characterized by Raman and X-ray photoelectron spectroscopy and visualized by electron microscopy and light scattering. The generation of reactive oxygen species was increased following dual NIR irradiation at 650nm and 808nm, which was attributed to the increased liberation of Ce6. In vitro, dual NIR irradiation significantly enhanced the anticancer effect of Ce6-incorporating AuNP by increasing the population of apoptotic cells. In vivo, tumor xenografted animals exhibited much better tumor suppression when subjected to dual NIR irradiation. Thus, we propose the use of Ce6-incorporating AuNP coupled to dual NIR irradiation for future anticancer treatment of solid tumors.

Multicomponent coassembled nanodrugs based on ovalbumin, pheophorbide a and Zn2+ for in vitro photodynamic therapy

Photodynamic therapy (PDT) has been considered as a therapeutic method based on non-invasiveness and lower side effect. However, photosensitizers (PS), as a major component of PDT, suffer from aggregation and limit reactive oxygen species (ROS) generation in the delivery process, thus causing unsatisfactory therapeutic effect of PDT. Herein, we demonstrate a multicomponent coordination coassembly strategy based on the combination of metal-binding protein (ovalbumin, OVA), metal ions (Zn2+) and a photosensitive drug (pheophorbide a, PheoA) for constructing supramolecular photosensitive nanodrugs towards antitumor PDT. The resulting photosensitizer nanodrugs exhibit well-defined nanorod structures, good colloidal dispersity, and high encapsulation efficiency. Most importantly, multicomponent coassembled nanorods possess favorable stability of physiological environment and on-demand release of PS in response to an acidic ambient in tumor cells. These features result in the high level of ROS generation in tumor cells, benefiting for enhanced therapeutic effect of in vitro PDT.

All-in-one hollow nanoformulations enabled imaging-guided Mn-amplified chemophototherapy against hepatocellular carcinoma

The drug resistance of hepatocellular carcinoma poses a great obstacle for chemotherapy as it severely undermines the clinical performance of common chemotherapeutics, and the implementation of nanotechnology-enabled combinational therapy offers new opportunities to circumvent this issue. Herein, an all-in-one hollow multi-component nanoformulation (aHNF) for hepatocellular carcinoma (HCC) treatment is reported, which could simultaneously load doxorubicin hydrochloride (Dox), chlorin e6 (Ce6) and manganic ions to realize Mn-amplified chemophototherapy. The loading strategy based on complexation effect and molecular selection establishes a simple yet effective platform for multi-component delivery via enhanced permeation and retention effect (EPR) and enables the sufficient release of photosensitizers to optimize the performance of photodynamic therapy (PDT). The co-delivery of Mn ions could elevate the cytotoxicity of both Dox and Ce6 via increasing the intracellular oxidative stress to damage cellular substructures and disrupt metabolic homeostasis. It also provides contrast for magnetic resonance imaging to guide the PDT treatment. This facile strategy allows to deliver multiple therapeutic modalities to hepatocellular carcinoma tissues, which then acts in synergy to overcome the treatment resistance of HCC and improves the antitumor activity.

Porphyrin‐Based Nanostructures for Cancer Theranostics: Chemistry, Fundamentals and Recent Advances

AbstractAs heterocyclic macrocycle organic compounds, porphyrins can generate a rich platform of chemical behavior and characteristics conveniently utilized for multiple bioapplications, including bio‐sensors, fluorescence tracking, and in vivo imaging. The conjugation of nanotechnology and porphyrins presents a promising approach to enhance the safety and effectiveness of porphyrin‐based materials in phototherapy against cancer. Several nanoformulations, including organic and inorganic nanocarriers, porphyrin‐laden nanoparticles, porphyrin‐based amphiphilic molecules, supramolecular polymers, and porphyrin‐based block copolymers, have been investigated to deliver porphyrins, which protect the pre‐mature release of photosensitizer and provide tumor‐selective and site‐specific targeting. The monodisperse nanoparticles formed of biocompatible building block conjugates can be beneficially used to develop a multifunctional novel system utilized in optical imaging, positron emission tomography, photodynamic therapy, photothermal therapy, and other imaging modalities in one formulation. This topic is important because exploiting and knowing porphyrin‐based nanostructures aids in detecting pathological damages that cannot readily be discovered by routine imaging or physical examination and thus, helps early diagnosis of cancer. This critical review will assess the basic knowledge and updated information for a broad audience of scientists, engineers, and newcomers related to the porphyrin‐based nanostructures for cancer theranostics

Dual antisense oligonucleotide targeting miR-21/miR-155 synergize photodynamic therapy to treat triple-negative breast cancer and inhibit metastasis

Triple negative breast cancer (TNBC) is a greatly aggressive subtype of breast cancer with high recurrence and mortality rates. Chemotherapy as a primary treatment for cancer is limited due to toxic side effects and drug resistance. Therefore, low toxicity and more effective breast cancer therapeutic approaches are greatly desired. In this study, a strategy which using ZIF-90 nanoparticles co-deliver Ce6-anti-miR-21 and Ce6-anti-miR-155 into the tumor cells was developed. Due to the pH responsive drug release of ZIF-90, antisense oligonucleotides (anti-miRNAs) and photosensitizers are able to be efficiently released inside tumor microenvironment. The nano delivery system captures overexpressed oncogenic miRNAs while the photosensitizer Ce6 generates ROS under light irradiation to effectively induce the apoptosis of tumor cell. This combinatorial effect was verified by results showing that the purposed therapic method could effectively inhibit tumor cell proliferation and metastasis. The concept of antisense oligonucleotide combined with photodynamic therapy has great potential in cancer treatment or adjuvant therapy.

A Sequential Dual‐Model Strategy Based on Photoactivatable Metallopolymer for On‐Demand Release of Photosensitizers and Anticancer Drugs (Adv. Sci. 23/2021)

Photoactivatable Metallopolymer In article number 2103334, Zhiyong Wei, Yang Li, Wen Sun, and co-workers demonstrate the on-demand release of photosensitizers and anticancer drugs based on photoactivatable metallopolymer Poly(Ru/PTX). Red light irradiation of polymer nanoparticles directly cleaves the Ru complex and produces 1O2 for photodynamic therapy, and sequentially, the generated 1O2 triggers the release of drugs for chemotherapy. This novel sequential dual-model release strategy creates a synergistic chemo-photodynamic therapy while minimizing the drug leakage.

A Sequential Dual-Model Strategy Based on Photoactivatable Metallopolymer for On-Demand Release of Photosensitizers and Anticancer Drugs.

The synergistic combination of chemotherapy and photodynamic therapy has attracted considerable attention for its enhanced antitumoral effects; however, it remains challenging to successfully delivery photosensitizers and anticancer drugs while minimizing drug leakage at off‐target sites. A red‐light‐activatable metallopolymer, Poly(Ru/PTX), is synthesized for combined chemo‐photodynamic therapy. The polymer has a biodegradable backbone that contains a photosensitizer Ru complex and the anticancer drug paclitaxel (PTX) via a singlet oxygen (1O2) cleavable linker. The polymer self‐assembles into nanoparticles, which can efficiently accumulate at the tumor sites during blood circulation. The distribution of the therapeutic agents is synchronized because the Ru complex and PTX are covalently conjugate to the polymer, and off‐target toxicity during circulation is also mostly avoided. Red light irradiation at the tumor directly cleaves the Ru complex and produces 1O2 for photodynamic therapy. Sequentially, the generated 1O2 triggers the breakage of the linker to release the PTX for chemotherapy. Therefore, this novel sequential dual‐model release strategy creates a synergistic chemo‐photodynamic therapy while minimizing drug leakage. This study offers a new platform to develop smart delivery systems for the on‐demand release of therapeutic agents in vivo.

Zinc pthalocyanine loaded poly (lactic acid) nanoparticles by double emulsion methodology for photodynamic therapy against 9 L/LacZ gliosarcoma cells

Development delivery systems, such as nanoparticles, represent a growing area in biomedical research. Nanoparticles (NP) were prepared using a double-emulsion method to load zinc(II) phthalocyanine (ZnPc). NP were obtained using poly (lactic acid) (PLA). ZnPc is a second generation of photosensitizer used in photodynamic therapy (PDT). ZnPc loaded PLA nanoparticles (NPLA-ZnPc) were prepared by double-emulsion method, characterized and available in cellular culture. The mean nanoparticle size presented particle size was 384.7 ± 84.2 nm with polydispersity index (PDI) of 0.150 ± 0.015, and the encapsulation efficiency was of 83%. The nanoparticle formulations presented negative zeta potential values (−27.5 ± 1.0 mV), explaining their colloidal stability. ZnPc loaded nanoparticles maintain its photophysical behavior after encapsulation. Photosensitizer release from nanoparticles was sustained over 168 h with a biphasic ZnPc release profile. An in vitro phototoxic effect in range of 80% was observed in 9 L/LacZ gliosarcoma cells at laser light doses (10 J cm−2) with 3.0 µg mL−1 of NPLA-ZnPc. All the physical–chemical, photophysical and photobiological measurements performed allow us to conclude that ZnPc loaded PLGA nanoparticles is a promising drug delivery system for PDT.

Photosensitive drug delivery systems for cancer therapy: Mechanisms and applications

Over the past three decades, various photosensitive nanoparticles have been developed as potential therapies in human health, ranging from photodynamic therapy technologies that have already reached clinical use, to drug delivery systems that are still in the preclinical stages. Many of these systems are designed to achieve a high spatial and temporal on-demand drug release via phototriggerable mechanisms. This review examines the current clinical and experimental applications in cancer treatment of photosensitive drug release systems, including nanocarriers such as liposomes, micelles, polymeric nanoparticles, and hydrogels. We will focus on the three main physicochemical mechanisms of imparting photosensitivity to a delivery system: i) photochemical reactions (oxidation, cleavage, and polymerization), ii) photoisomerization, iii) and photothermal reactions. Photosensitive nanoparticles have a multitude of different applications including controlled drug release, resulting from physical/conformational changes in the delivery systems in response to light of specific wavelengths. Most of the recent research in these delivery systems has primarily focused on improving the efficacy and safety of cancer treatments such as photodynamic and photothermal therapy. Combinations of multiple treatment modalities using photosensitive nanoparticulate delivery systems have also garnered great interest in combating multi-drug resistant cancers due to their synergistic effects. Finally, the challenges and future potential of photosensitive drug delivery systems in biomedical applications is outlined.