Hypoxia photodynamic therapy

The efficacy of photodynamic therapy (PDT) is highly dependent on the photosensitizer features. The reactive oxygen species (ROS) generated by photosensitizers is proven to be associated with immunotherapy by triggering immunogenic cell death (ICD) as well. In this work, we establish a rhodamine-iridium(III) hybrid model functioning as a photosensitizer to comprehensively understand its performance and potential applications in photodynamic immunotherapy. Especially, the correlation between the ROS generation efficiency and the energy level of the Ir(III)-based excited state (T1 '), modulated by the cyclometalating (C∧ N) ligand, is systematically investigated and correlated...

Photodynamic therapy (PDT) exhibits great application prospects in future clinical oncology due to its spatiotemporal controllability and good biosafety. However, the antitumor efficacy of PDT is seriously hindered by many factors, including tumor hypoxia, limited light penetration ability, and strong defense mechanisms of tumors. Considering that it is difficult to completely solve the first two problems, enhancing the lethality of antitumor PDT has become a good idea to extend its clinical application. Herein, we summarize the nanoplatform-involved strategies to effectively amplify the tumoricidal capability of current PDT and then discuss the present bottlenecks and prospects of the nanoplatform-based PDT sensitization strategies in tumor therapy...

The multifaceted nature of photodynamic therapy (PDT) requires a throughout evaluation of a multitude of parameters when devising preclinical protocols. In this study, we constructed MCF-7 human breast tumor spheroid assays to infer PDT irradiation doses at four gradient levels for violet light at 408 nm and red light at 625 nm under normal and hypoxic oxygen conditions. The compacted three-dimensional (3D) tumor models conferred PDT resistance as compared to monolayer cultures due to heterogenous distribution of photosensitizers along with the presence of internal hypoxic region...

Non-invasive therapies such as photodynamic therapy (PDT) and chemodynamic therapy (CDT) have received wide attention due to their low toxicity and side effects, but their efficacy is limited by the tumor microenvironment (TME), and monotherapy cannot achieve satisfactory efficacy. In this work, a multifunctional nanoparticle co-assembled from oleanolic acid (OA), chlorin e6 (Ce6) and hemin was developed. The as-constructed nanoparticle named OCH with diameters of around 130 nm possessed good biostability, pH/GSH dual-responsive drug release properties, and remarkable cellular internalization and tumor accumulation capabilities...

PURPOSE: Photodynamic therapy (PDT) has been an attractive strategy for skin tumor treatment. However, the hypoxic microenvironment of solid tumors and further O2 consumption during PDT would diminish its therapeutic effect. Herein, we developed a strategy using the combination of PDT and hypoxia-activated bioreductive drug tirapazamine (TPZ). METHODS: TPZ was linked to DSPE-PEG-NHS forming DSPE-PEG-TPZ to solve leakage of water-soluble TPZ and serve as an antitumor agent and monomer molecule further forming the micellar...

Hypoxic tumor microenvironment (TME) hampers the application of oxygen (O2 )-dependent photodynamic therapy (PDT) in solid tumors. To address this problem, a biomimetic nanotheranostics (named MMCC@EM) is developed for optical molecular imaging-escorted self-oxygenation PDT. MMCC@EM is synthesized by encapsulating chlorin e6 (Ce6) and catalase (CAT) in metal-organic framework (MOF) nanoparticles with erythrocyte membrane (EM) camouflage. Based on the biomimetic properties of EM, MMCC@EM efficiently accumulates in tumor tissues...

The combination of photodynamic (PDT) and chemodynamic therapy (CDT) for cancer treatment has gathered a lot of attention in recent years. However, its efficacy is severely limited by elevated levels of hypoxia and glutathione (GSH) in the tumor microenvironment (TME). Multifunctional nanoparticles that can help remodel the TME while facilitating PDT/CDT combination therapy are the need of the hour. To this effect, we have developed O2 self-supplying, free radical generating nanohybrids that exhibit NIR triggered photothermal (PTT)/photo-induced thermodynamic (P-TDT) and chemodynamic therapy for efficient breast cancer treatment...

Recent years have witnessed dramatic improvements in nanotechnology-based cancer therapeutics, and it continues to evolve from the use of conventional therapies (chemotherapy, surgery, and radiotherapy) to increasingly multi-complex approaches incorporating thermal energy-based tumor ablation ( e.g. magnetic hyperthermia and photothermal therapy), dynamic therapy ( e.g. photodynamic therapy), gene therapy, sonodynamic therapy ( e.g. ultrasound), immunotherapy, and more recently real-time treatment efficacy monitoring ( e...

Hypoxia is characteristic of the tumor microenvironment, which is correlated with resistance to photodynamic therapy (PDT), radiotherapy, chemotherapy, and immunotherapy. Catalase is potentially useful to catalyze the conversion of endogenous H2 O2 to O2 for hypoxia reversion. However, the efficient delivery of catalase into the hypoxia regions of tumors is a huge challenge. Here, we report the self-assembly of ultra-acid-sensitive polymer conjugates of catalase and albumin into nanomicelles that are responsive to the acidic tumor microenvironment...

We use low-molecular-weight branched polyethylenimine (PEI) to produce cytocompatible reduced graphene oxide quantum dots (rGOQD) as a photothermal agent and covalently bind it with the photosensitizer IR-820. The rGOQD/IR820 shows high photothermal conversion efficiency and produces reactive oxygen species (ROS) after irradiation with near-infrared (NIR) light for photothermal/photodynamic therapy (PTT/PDT). To improve suspension stability, rGOQD/IR820 was PEGylated by anchoring with the DSPE hydrophobic tails in DSPE-PEG-Mal, leaving the maleimide (Mal) end group for covalent binding with manganese dioxide/bovine serum albumin (MnO2 /BSA) and targeting ligand cell-penetrating peptide (CPP) to synthesize rGOQD/IR820/MnO2 /CPP...

Photodynamic therapy (PDT) has been approved for clinic. However, powerless efficiency for deep hypoxic tumor therapy remains an enormous challenge for PDT. Herein, a hypoxia-sensitive nanotherapeutic system (FTCD-SRGD) based on fullerene (C70 ) and anoxic activating chemical prodrug tirapazamine (TPZ) is rationally designed for multimodal therapy of deep hypoxic tumors. To enhance the accumulation and achieve specific drug release in tumor, the FTCD-SRGD is modified with cyclo(Arg-Gly-Asp-d-Phe-Lys) (cRGDfK) peptide and disulfide bonds...

Antibacterial photodynamic therapy (aPDT) is highly effective in killing bacteria, while the problem of hypoxia and limited light penetration in deep tissue has not been properly solved. In addition, few aPDT works take into account the regulation of inflammation, which is an important regulatory process after antimicrobial therapy and the final purpose of treatment. In this work, to address the above isssues, we have designed a multi-functional composite UCNPs-Ce6-Mn(CO)5 Br@Silane (referred to as UCM@Si), which consists of several key components: Up-conversion nanoparticles (UCNPs: NaErF4 :Tm3+ @NaYF4 :Yb3+ ), Chlorin e6 (Ce6) and Manganese pentacarbonyl bromide (Mn(CO)5 Br)...

Functionalized with the Au-S bond, gold nanoflares have emerged as promising candidates for theranostics. However, the presence of intracellular abundantly biothiols compromises the conventional Au-S bond, leading to unintended release of cargoes and associated side-effects on non-target cells. Additionally, hypoxic microenvironment in diseased regions limits treatment efficacy, particularly in dynamic therapy. To address these challenges, high-fidelity photodynamic nanoflares constructed on Pt-coated gold nanoparticles (Au@Pt PDNF) were communicated to avoid false-positive therapeutic signals and side-effects caused by biothiol perturbation...

Hypoxia as an inherent feature in tumors is firmly associated with unsatisfactory clinical outcomes of photodynamic therapy (PDT) since the lack of oxygen leads to ineffective reactive oxygen species (ROS) productivity for tumor eradication. In this study, an oxidative phosphorylation (OXPHOS) targeting nanoplatform was fabricated to alleviate hypoxia and enhance the performance of PDT by encapsulating IR780 and OXPHOS inhibitor atovaquone (ATO) in triphenylphosphine (TPP) modified poly(ethylene glycol) methyl ether-block-poly(L-lactide-co-glycolide) (mPEG-PLGA) nanocarriers (TNPs/IA)...

INTRODUCTION: Tumor hypoxia and invasion present significant challenges for the efficacy of photodynamic therapy (PDT) in triple-negative breast cancer (TNBC). This study developed a mitochondrial targeting strategy that combined PDT and gene therapy to promote each other and address the challenges. METHODS: The positively charged amphiphilic material triphenylphosphine-tocopherol polyethylene glycol succinate (TPP-TPGS, TPS) and the photosensitizer chloride e6 (Ce6) formed TPS@Ce6 nanoparticles (NPs) by hydrophobic interaction...

This review discusses the possible methods for improving therapeutic efficacies of phthalocyanine (Pcs) -based therapeutic probes in photo- and sono-dynamic therapies under hypoxic conditions. Herein, the structural design strategies including varying the central metal, position substituents and the effects of adjuvant used in supplementing the therapeutics activities of Pcs or formation of NPs are discussed for cancer therapies in hypoxic conditions. Different mechanisms induced for cell death influenced by the compositions of the Pcs-probes are discussed...

Tumor hypoxia impairs the generation of reactive oxygen species and the induction of immunogenic cell death (ICD) for photodynamic therapy (PDT), thus impeding its efficacy and the subsequent immunotherapy. In addition, hypoxia plays a critical role in forming immunosuppressive tumor microenvironments (TME) by regulating the infiltration of immunosuppressive tumor-associated macrophages (TAMs) and the expression of programmed death ligand 1 (PD-L1). To simultaneously tackle these issues, a MnO2 -containing albumin nanoplatform co-delivering IR780, NLG919, and a paclitaxel (PTX) dimer is designed to boost photodynamic immunotherapy...

A synergistic therapy agent (STA) with photothermal, photodynamic, chemodynamic, and starvation therapy (PTT, PDT, CDT, and ST) functions was developed. Hollow, mesoporous, and nearly uniform CeO2 nanoparticles (H-CeO2 NPs) were synthesized using a staged shape templating sol-gel protocol. Chlorin e6 (Ce6) was adsorbed onto H-CeO2 NPs, and a thin polydopamine (PDA) layer was formed on Ce6-adsorbed H-CeO2 NPs. Glucose oxidase (GOx) was bound onto PDA-coated Ce6-adsorbed H-CeO2 NPs to obtain the targeted STA (H-CeO2 @Ce6@PDA@GOx NPs)...

Cancer metastasis and invasion are closely related to tumor cell immunosuppression and intracellular hypoxia. Activation of immunogenicity and intracellular oxygenation are effective strategies for cancer treatment. In this study, multifunctional nanomicelle hyaluronic acid and cinnamaldehyde is self-assembled into nanomicelles (HPCNPs) were constructed for immunotherapy and tumor cell oxygenation. The Schiff base was constructed of HPCNPs with pyropheophorbide a-Cu (PPa-Cu). HPCNPs are concentrated in tumor sites under the guidance of CD44 proteins, and under the stimulation of tumor environment (weakly acidic), the Schiff base is destroyed to release free PPa...

Hypoxia is a critical factor for restricting photodynamic therapy (PDT) of tumor, and it becomes increasingly severe with increasing tissue depth. Thus, the relief of deep tumor hypoxia is extremely important to improve the PDT efficacy. Herein, tumor microenvironment (TME)-responsive size-switchable hyaluronic acid-hybridized Ru nanoaggregates (HA@Ru NAs) were developed via screening reaction temperature to alleviate deep tumor hypoxia for improving the tumor-specific PDT by the artful integration multiple bioactivated chemical reactions in situ and receptor-mediated targeting (RMT)...