Self‐Amplified Photodynamic Therapy through the ¹O₂‐Mediated Internalization of Photosensitizers from a Ppa‐Bearing Block Copolymer

Abstract

Nanocarriers are employed to deliver photosensitizers for photodynamic therapy (PDT) through the enhanced penetration and retention effect, but disadvantages including the premature leakage and non‐selective release of photosensitizers still exist. Herein, we report a 1O2‐responsive block copolymer (POEGMA‐b‐P(MAA‐co‐VSPpaMA) to enhance PDT via the controllable release of photosensitizers. Once nanoparticles formed by the block copolymer have accumulated in a tumor and have been taken up by cancer cells, pyropheophorbide a (Ppa) could be controllably released by singlet oxygen (1O2) generated by light irradiation, enhancing the photosensitization. This was demonstrated by confocal laser scanning microscopy and in vivo fluorescence imaging. The 1O2‐responsiveness of POEGMA‐b‐P(MAA‐co‐VSPpaMA) block copolymer enabled the realization of self‐amplified photodynamic therapy by the regulation of Ppa release using NIR illumination. This may provide a new insight into the design of precise PDT.

Advances in photosensitizer-related design for photodynamic therapy

“…Ppa is a derivative of chlorophyll, which are the most abundant natural photosynthetic pigments [41] . This photosensitizer is named POEGMA-b-P (MAA-co-VSPpaMA), which could intelligently release ROS when the host NPs accumulate in tumor tissue and is dissolved by cancer cells [42] . The photosensitizer Ppa was functionalized with a 1 O 2 -responsive vinyldithioether [43] ( Fig.…”

“… Photosensitizer system Treatment effect Combo Radiation source Ref. CuS@ICG This system aims to both kill tumor cells and disrupt the tumor microenvironment for enhanced tumor suppression PDT and PTT 808 nm laser [30] Ppa Ppa is a derivative of chlorophyll, which are the most abundant natural photosynthetic pigments – 660 nm-light irradiation [41] Responsive NPs including Ppa was designed, It could intelligently release ROS – [42] The photosensitizer Ppa was functionalized with a 1 O 2 -responsive vinyldithioether – [43] Chlorin I & II The structures of those two compounds are also stable under photo-bleaching test, and in vivo assessments displayed that they both have high tumor selectivity – Absorption peak around 650 nm [44] NP-sfb/ce6 This system is a combination of immunotherapy and PDT, and it appears that the synergistic treatment of tumor is more effective than single cancer treatment PDT and immunotherapy 660 nm-light irradiation [46] 5-ALA 5-ALA, a precursor of porphyrin, is reported to delay glioma progression and is expected to have great potential in PDT. – 410, 510, 545, 580 and 630 nm under 405 nm + 505 nm light source, 5-ALA as photodynamic drug produced the most ROS [49] A nano delivery system where 5-ALA is loaded on PMO with PB coating (PB@PMO-5-ALA), It increased PpIX level in glioma cells by 75% comparing with unprotected 5-ALA in mice.…”

Recent near-infrared light-activated nanomedicine toward precision cancer therapy

“…90 For the former, arylboronic ester, dithioketal, dialkoxy anthracene, and vinyldithio ether derivatives, which would be cleaved by ROS oxidation, are commonly used as linkers for on-demand delivery. [91][92][93][94][95][96][97][98][99][100] For example, based on an arylboronic ester, Xu's group has designed an ROS-sensitive cyclodextrin derivative to encapsulate DOX and a photosensitizer (purpurin 18). 99 Besides the ROS in the tumor microenvironment, NIR laser illumination also contributed to the release of DOX owing to the ROS generation from purpurin 18 upon NIR illumination.…”

Study of copper-cysteamine based X-ray induced photodynamic therapy and its effects on cancer cell proliferation and migration in a clinical mimic setting

“…With the development of nanotechnology, photodynamic therapy (PDT) has emerged as an efficient treatment method for cancer patients with many advantages, including fewer side effects to normal tissues and high selectivity [ [3] , [4] , [5] ]. Nevertheless, ultraviolet (UV), visible light or near-infrared (NIR) light-induced PDT has the characteristics of low tissue penetration and rapid energy decay.…”