Asymmetric silicon phthalocyanine based nanoparticle with spatiotemporally targeting of mitochondria for synergistic apoptosis-ferroptosis antitumor treatment.

A promising therapeutic strategy in cancer treatment merges photodynamic therapy (PDT) induced apoptosis with ferroptosis, a form of programmed cell death governed by iron-dependent lipid peroxidation. Given the pivotal role of mitochondria in ferroptosis, the development of photosensitizers that specifically provoke mitochondrial dysfunction and consequentially trigger ferroptosis via PDT is of significant interest. To this end, we have designed and synthesized a novel nanoparticle, termed FECTPN, tailored to address this requisite. FECTPN harnesses a trifecta of critical attributes: precision mitochondria targeting, photoactivation capability, pH-responsive drug release, and synergistic apoptosis-ferroptosis antitumor treatment. This nanoparticle was formulated by conjugating an asymmetric silicon phthalocyanine, Chol-SiPc-TPP, with the ferroptosis inducer Erastin onto a ferritin. The Chol-SiPc-TPP is a chemically crafted entity featuring cholesteryl (Chol) and triphenylphosphine (TPP) functionalities bonded axially to the silicon phthalocyanine, enhancing mitochondrial affinity and leading to effective PDT and subsequent apoptosis of cells. Upon cellular uptake, FECTPN preferentially localizes to mitochondria, facilitated by Chol-SiPc-TPP's targeting mechanics. Photoactivation induces the synchronized release of Chol-SiPc-TPP and Erastin in the mitochondria's alkaline domain, driving the escalation of both ROSs and lipid peroxidation. These processes culminate in elevated antitumor activity compared to the singular application of Chol-SiPc-TPP-mediated PDT. A notable observation is the pronounced enhancement in glutathione peroxidase-4 (GPX4) expression within MCF-7 cells treated with FECTPN and subjected to light exposure, reflecting intensified oxidative stress. This study offers compelling evidence that FECTPN can effectively induce ferroptosis and reinforces the paradigm of a synergistic apoptosis-ferroptosis pathway in cancer therapy, proposing a novel route for augmented antitumor treatments.

Fluorinated triphenylamine silicon phthalocyanine nanoparticles with two-color imaging guided in vitro photodynamic therapy through lysosomal dysfunction.

Lysosome-targeting therapy has emerged as a promising strategy for combating drug-resistant tumors. However, the synthesis of nanodrugs to achieve efficient lysosome targeting remains a challenging task. In this study, a nanoparticle DSPE@TPA-FBPA-SiPc was developed for lysosome targeting therapy. The nanoparticle was prepared by loading 2-[4-(diphenylamino)-1-diphenicacid-1-carbobenzoxy-4-(1,1,1,3,3,3-hexafluoropropane-4-phenoxy) silicon phthalocyanine (TPA-FBPA-SiPc) into 1,2-distearoyl-sn­glycero-3-phosphoethanolamine-N-[succinyl(polyethyleneglycol)-2000] (DSPE). DSPE@TPA-FBPA-SiPc demonstrated remarkable capabilities such as two-color imaging, lysosome targeting and in vitro photodynamic therapy functions. The results revealed that DSPE@TPA-FBPA-SiPc efficiently accumulated in lysosomes, leading to generation of a high amount of reactive oxygen species upon irradiation. This induced apoptosis in MCF-7 cells by disrupting lysosomal function. Consequently, DSPE@TPA-FBPA-SiPc holds great potential as a photosensitizer for photodynamic therapy, utilizing the lysosomal-mediated cell death pathway.

Chlorophenyl thiophene silicon phthalocyanine: Synthesis, two-photon bioimaging-guided lysosome target, and in vitro photodynamic efficacy.

The development of efficient photosensitizers with high singlet oxygen quantum yield, strong fluorescent emission, excellent photostability, and specific organelle targeting is in great demand for the enhancement of PDT treatment efficiency. This study designed and synthesized a new two-photon photosensitizer chlorophenyl thiophene axially substituted silicon (IV) phthalocyanine (CBT-SiPc). CBT-SiPc showed specific targeting of lysosomes in living cells and good biocompatibility. Furthermore, high 1O2 generation efficiency and high PDT efficiency in MCF-7 breast cancers under irradiation were also demonstrated. The novel CBT-SiPc showed great potential in the application of lysosome-targeted and two-photon bioimaging-guided photodynamic cancer therapy.