Photodynamic therapy (PDT) is an emerging therapeutic modality for malignant cancers as it generates cytotoxic reactive oxygen species (ROS) and stimulates immune responses.  

PDT-based oncotherapy is triggered by irradiating a type of photoactive agents, photosensitizers. However, the clinical applications of PDT are generally limited by the drawbacks of photosensitizers.

In a recent study published in ACS Applied Materials & Interfaces, Prof. CHEN Zhuo's group at Fujian Institute of Research on the Structure of Matter of Chinese Academy of Sciences reported the controllable photodynamic effects by using a type of smart photodynamic nanodots, pentalysine-phthalocyanine assembly nanodots (PPAN).

Fabricated by an amphipathic conjugate of a phthalocyanine-based photosensitizer and a pentalysine peptide, PPAN demonstrated a spherical configuration with a highly positive shell and hydrophobic core. The PDT effects of PPAN can be precisely controlled by the disintegration of the nanodots.

In circulation systems, PPAN demonstrated the assembly configuration, which efficiently declines the renal clearance and the off-target photodynamic effects.

In contrast, when PPAN contacts with tumor tissues, the assembly configuration disintegrates, and the monomeric photosensitizer molecules are released consequently. The released photosensitizers thus perform PDT effects for the clearance of cancer cells.

Another highlight of this study was the simulation of the processes of self-assembly using the molecular dynamic simulations, which revealed the assembly mechanism of PPAN and certified the design strategy.

The development of self-assembly PPAN provided a novel strategy to improve the biocompatibility of clinical photosensitizers and a new concept of precisely controlling the occurrence of PDT effects.

Schematic representation of the tumor-triggered PDT by self-assembled pentalysine-Pc assembly nanodots (PPAN). (Image by Prof. CHEN’s Group)