Polymeric micelles in advanced photodynamic therapy: Design, delivery and translational prospects

Photodynamic therapy (PDT) is widely studied and complex method useful as a minimally invasive cancer treatment strategy, relying on photosensitizers (PSs), light, and oxygen to induce cytotoxicity. Indeed, the controlled delivery of conventional PSs is the key factor in achieving effective treatment outcome. Among many drug delivery systems, the polymeric micelles represent a promising platform to address the solubility, stability, and delivery challenges associated with PSs. The design of micelles, constructed from hydrophilic and hydrophobic polymeric blocks in diverse structures, enables precise tailoring of carrier properties to optimize PS delivery. This paper focuses on the potential applications and limitations of polymer micelles for the controlled delivery of PSs in the field anticancer therapy. Various methods of synthesis, incorporation of PSs as well as their release and activation are described in detail. The effect of micellar system employment on circulation time, off-target effects, and both passive and active targeting are thoroughly depicted. Despite the clinical promise, the limitations of PDT including shallow tissue penetration and restricted applicability to superficial or endoscope-accessible tumors are discussed, as well as the future prospects consisting in red-shifted or two-photon absorption systems.