Aug 2026· ChemistrySelect· Vol 11· 0 citations· 160 references
TL;DR
This review highlights mechanisms, recent advances, and translational challenges of natural PS‐based nanotherapeutics across multiple cancers, emphasizing strategies to improve delivery, selectivity, and therapeutic outcomes for next‐generation PDT.
Abstract
Photodynamic therapy (PDT) is a minimally invasive cancer treatment that uses photosensitizers (PSs), light, and oxygen to generate cytotoxic reactive oxygen species. Natural product‐derived PSs, including alkaloids, flavonoids, polyphenols, curcuminoids, perylenequinones, phycocyanin, and anthraquinones, offer advantages such as biocompatibility and low toxicity but are limited by poor solubility, stability, and targeting. Nanotherapeutic systems such as organic, inorganic, and carbon‐based nanoparticles, nanogels, hydrogels, lipid carriers, and nanoemulsions address these limitations by enhancing stability, tumor accumulation, and controlled release. These platforms also enable multifunctional approaches, including imaging‐guided PDT, combination therapies, and stimuli‐responsive activation. This review highlights mechanisms, recent advances, and translational challenges of natural PS‐based nanotherapeutics across multiple cancers, emphasizing strategies to improve delivery, selectivity, and therapeutic outcomes for next‐generation PDT.
Natural photosensitizers have emerged as promising candidates for photodynamic therapy (PDT) owing to their structural diversity, favorable biocompatibility, and broad biological activities. However, their significance extends beyond their natural origin, as they represent the products of chemo‐biodiversity shaped by millions of years of evolutionary adaptation to diverse ecological pressures. This review examines natural photosensitizers through a chemo‐biodiversity perspective, emphasizing how evolutionary diversification has generated structurally distinct photoactive scaffolds with unique photophysical and photobiological properties relevant to cancer therapy. Attention is given to the relationships between molecular architecture, excited‐state dynamics, reactive oxygen species generation, and therapeutic performance, highlighting how structural features govern photodynamic efficiency and biological responses. The review further discusses how nanotechnology‐based engineering strategies can overcome intrinsic limitations, including poor aqueous solubility, aggregation, photoinstability, and limited tumor selectivity. Recent advances in multifunctional nanoplatforms, molecular engineering, and combination therapies are critically evaluated alongside current translational challenges, including manufacturing, regulatory considerations, and clinical development. By integrating natural product chemistry, photophysics, photobiology, and nanotechnology within a unified conceptual framework, this review demonstrates that chemo‐biodiversity provides a rational foundation for the discovery of next‐generation natural photosensitizers. Harnessing nature's evolutionary molecular diversity offers new opportunities to develop safer, more effective, and clinically translatable photodynamic therapies.
I. Baidoo, H. Abrahamse, B. George· Chemistry and Biodiversity· 0 citations
The escalating global cancer burden, particularly in low- and middle-income countries, necessitates safer and more effective therapeutic strategies. The toxicity and environmental issues of traditional heavy-metal-based quantum dots (QDs) have been addressed by green-synthesised QDs, which have become a promising platform for nanomedicine. In photodynamic treatment (PDT), photothermal therapy (PTT), and theranostic applications, the anticancer effectiveness of green-synthesized QDs that are derived from plant extracts, microbes, biomolecules, and biomass waste is critically assessed. Green synthesis techniques, such as hydrothermal and microwave-assisted methods, provide biocompatible QDs with good photostability, tunable optical characteristics, and decreased cytotoxicity. Mechanistically, these QDs generate reactive oxygen species (ROS), induce mitochondrial dysfunction, produce localized hyperthermia upon near-infrared irradiation, and activate apoptotic pathways (such as p53, Bax/Bcl-2, and caspase cascade), leading to selective cancer cell death. Preclinical in vitro and in vivo studies demonstrate potent tumor ablation through passive (EPR effect) and active targeting strategies. Despite these advances, some key setbacks hinder their clinical translation: lack of standardized synthesis protocols, batch-to-batch variability, limited long-term biosafety data, suboptimal targeting efficiency, and regulatory hurdles. Future perspectives include AI-driven optimization, smart theranostic platforms integrating multimodal imaging and therapy, and sustainable circular economy approaches using biowaste. Addressing these challenges through harmonized protocols and rigorous preclinical validation will be essential to realize the full potential of green-synthesized QDs as safe, multifunctional, and effective cancer nanomedicines.
G. Kah, Heidi Abrahamse· RSC Advances· 0 citations
Overall, PDT combination design should be guided by whether adjunctive agents support or undermine photosensitizer accumulation, oxygen availability, ROS-mediated cytotoxicity, and immune activation, when selected according to mechanistic compatibility.
Ilaf Naser, D. Bartusik-Aebisher, Barbara Smolak et al.· Biomedicines· 0 citations
This review constructs a refined mechanistic framework to elaborate the complementary mechanisms of PDT and PTT toward CDT in terms of reaction kinetics modulation, endogenous substrate replenishment, and tumor antioxidant defense inhibition, and the key bottlenecks hindering clinical translation.
Yuxuan Ma, Jie Gong, Zixuan Wu et al.· International Journal of Nan...· 0 citations
Skin cancer is a highly heterogeneous malignancy with increasing incidence and limited therapeutic efficacy from conventional treatments due to poor specificity, inadequate drug penetration, and resistance. Nanomaterial-based platforms have emerged as promising strategies to address these challenges by enabling precise diagnosis and targeted therapy. This review summarizes recent advances in nanomaterial-mediated theranostics for skin cancer, including organic, inorganic, and biomimetic or hybrid nanosystems. Their roles in enhancing drug delivery through passive and active targeting, improving transdermal penetration, and enabling controlled release are highlighted. Emerging diagnostic approaches based on nanotechnology, such as imaging and biosensing, are also discussed for sensitive and noninvasive detection. In addition, nanoplatform-enabled multimodal therapies that integrate chemotherapy, phototherapy, gene therapy, and immunotherapy are presented, with particular emphasis on microneedle-assisted transdermal systems. Despite the remaining challenges in terms of biosafety, scalability, and clinical translation, nanomaterials offer significant potential for advancing precise and personalized skin cancer management.
Yu-Lung Hsieh, Jun Xie, Shaohua Jiang et al.· Journal of materials chemist...· 0 citations
Photodynamic therapy (PDT) is a minimally invasive cancer treatment strategy. Despite numerous studies confirming its potential advantages, the clinical translation of this technique remains limited owing to the impracticality of using conventional light sources and the instability of photosensitizers. This study presents a novel PDT approach that utilizes organic light-emitting diodes (OLEDs) as compact, low-thermal, wearable, and flexible light sources to activate chlorin e6 (Ce6)-loaded Pluronic nanocapsules (Ce6/Plu NCs) for anticancer therapy. Here, different types of Pluronic polymers are used and optimized to synthesize ∼120 nm-diameter Ce6/Plu NCs. Among the formulated systems, the Ce6/PP123 NCs show optimal spectral characteristics and the highest therapeutic efficacy in vitro, and efficient tumor accumulation after intravenous injection and significant antitumor efficacy upon OLED irradiation with minimal off-target toxicity in vivo. Tissue-attachable OLEDs for PDT can be placed in close proximity to tumor tissue for efficient light delivery. The combination of the Ce6/PP123 NCs with a novel wearable OLED is a promising platform for effective and safe PDT in cancer treatment.
Hyeryeon Oh, S. Jeong, Cheol Hui Park et al.· Advanced Healthcare Material...· 0 citations