Overview of Nanoparticle-Based Approaches for the Combination of Photodynamic Therapy (PDT) and Chemotherapy at the Preclinical Stage

SIMPLE SUMMARY: The present review represents the outstanding and promising recent literature reports (2017–2022) on nanoparticle-based formulations developed for anticancer therapy with photodynamic therapy (PDT), photosensitizers, and chemotherapeutics. Besides brief descriptions of chemotherapeutics’ classification and of PDT mechanisms and limitations, several examples of nanosystems endowed with different responsiveness (e.g., acidic pH and reactive oxygen species) and peculiarity (e.g., tumor oxygenation capacity, active tumor targeting, and biomimetic features) are described, and for each drug combination, in vitro and in vivo results on preclinical cancer models are reported. ABSTRACT: The widespread diffusion of photodynamic therapy (PDT) as a clinical treatment for solid tumors is mainly limited by the patient’s adverse reaction (skin photosensivity), insufficient light penetration in deeply seated neoplastic lesions, unfavorable photosensitizers (PSs) biodistribution, and photokilling efficiency due to PS aggregation in biological environments. Despite this, recent preclinical studies reported on successful combinatorial regimes of PSs with chemotherapeutics obtained through the drugs encapsulation in multifunctional nanometric delivery systems. The aim of the present review deals with the punctual description of several nanosystems designed not only with the objective of co-transporting a PS and a chemodrug for combination therapy, but also with the goal of improving the therapeutic efficacy by facing the main critical issues of both therapies (side effects, scarce tumor oxygenation and light penetration, premature drug clearance, unspecific biodistribution, etc.). Therefore, particular attention is paid to the description of bio-responsive drugs and nanoparticles (NPs), targeted nanosystems, biomimetic approaches, and upconverting NPs, including analyzing the therapeutic efficacy of the proposed photo-chemotherapeutic regimens in in vitro and in vivo cancer models.