Synthesis and optimization of ZnPc-loaded biocompatible nanoparticles for efficient photodynamic therapy

Zinc(II) phthalocyanine (ZnPc) is a promising photosensitizer for PDT but suffers from aggregation in a physiological aqueous environment. In this paper, a class of biocompatible polymeric nanoparticles (NPs) was prepared to encapsulate ZnPc molecules. Mostly because of the planar structure, ZnPc molecules were difficult to be encapsulated into the polymeric NPs unless further coated with a thick poly-L-lysine (PLL) layer. The PLL shell endowed the NPs with good biocompatibility, efficient cellular uptake, and potential bioconjugation. The degree of aggregation (DOA) of ZnPc molecules in PLL-NPs was thoroughly investigated based on self-defined relative DOA, and a loading capacity of 4 wt% was deduced as the turning point for aggravating aggregation. Similarly, the optimal loading capacity of ZnPc was determined to be 4% according to the 1O2 generation rate, demonstrating the feasibility of the DOA approach. Polymers with large rigid units (PVK and PFO) were also utilized to relieve the aggregation of ZnPc in NPs. Taking advantage of the optimized ZnPc-loaded NPs, high PDT efficacy was demonstrated in HepG2 cells and in tumor-bearing mice as well. Both high in vitro and in vivo PDT efficacy and biocompatibility are demonstrated. Aside from affording a class of efficient biocompatible nanophotosensitizers, this work is also instructive to design other types of ZnPc-based nanocarriers, in which aggregation should be well considered.