Fig. 7 Porphyrin self-assembled nanoparticles restrict porphyrin aggregation to enhance PDT. Advantages: a. Limited tetraphenylporphyrin precipitates b. High 1O2 generation efficiency
On this basis, Jin and co-workers prepared alternating copolymers (P(MIPOSS-alt-VBTPP)-b-POEGMA) using 4-vinylbenzyl terminal tetraphenylporphyrin (VBTPP) and maleimide isobutyl polyhedral oligomeric sesquioxane (MIPOSS) as starting monomers by alternating reversible addition-rupture chain transfer (RAFT) polymerization(Jin et al. 2018). In which porphyrins and polyhedral oligo-sesquisiloxanes (POSS) are alternately mounted on the main chain. They self-assemble into nanoparticles in water. The aggregation-induced quenching (AIQ) phenomenon among the porphyrin units can be effectively reduced by the spatial cage structure and alternating structure of the POSS units. In vitro dark cytotoxicity and phototoxicity assays. Cells treated with 50 μg/mL of polymer nanoparticles (concentration of porphyrin) showed no significant dark cytotoxicity. At a concentration of 25 μg/mL, the phototoxicity of PM nanoparticles without POSS units (control group) was significantly lower than that of the experimental group. This result indicated that the POSS units with spatial cage structure in the block copolymer could effectively improve the photocatalytic efficiency. The group further evaluated the in vivo efficacy of PDT by intravenous injection. The results showed that the tumors of both nanoparticle-treated mice were inhibited, and the tumors of one group of experimentally treated mice were almost eradicated. This suggests that P(MIPOSS-alt-VBTPP)-b-POEGMA with a spatial cage-like structure has better PDT efficacy.
Although several approaches have been developed to reduce aggregation-induced quenching, such as using POSS units on polymer side chains to isolate tetraphenylporphyrin (TPP) or developing tree-like macromolecules around TPP, the drug loading capacity (LC) of PS is relatively low due to the additional introduction of redundant non-therapeutic groups(Ideta et al. 2005; Jin et al. 2018). zheng and co-workers developed the first poly TPP nanoparticles prepared by cross-linking degradable reactive oxygen clusters, thiometallic linkers, and tetraphenylporphyrin derivatives, followed by co-precipitation(Zheng et al. 2019). With quantitative loading efficiency (>99%), homogeneous nanoparticles (no aggregation), and increased quantum yield of 1O2Δ = 0.79 in dimethyl sulfoxide compared to 0.52 for the original TPP). The results of the in vivo antitumor effect study of nanoparticles showed that poly TPP nanoparticles could effectively accumulate at the tumor site after 8 h of injection. 650 nm lighted TPP nanoparticles showed significant inhibition of tumor growth, and the tumor volume was about 1/10 of that in the PBS group after 10 d. In contrast, poly TPP nanoparticles showed the best therapeutic effect and significant inhibition of tumor growth. Finally, the volume of the poly TPP nanoparticles group was almost 1/5 of the original volume and 1/50 of the PBS group. This is sufficient to demonstrate the efficient drug release and excellent in vivo antitumor effect of poly TPP nanoparticles under red light irradiation.