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 1O2 (ΦΔ = 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.