Peptide 18-4/chlorin e6-conjugated polyhedral oligomeric silsesquioxane nanoparticles for targeted photodynamic therapy of breast cancer.

Chlorin e6 (Ce6), with its high phototoxic potential, has wide applications in photodynamic therapy (PDT) for many human diseases. However, poor cancer cell localization of Ce6 has limited its direct application for PDT. Here, we developed cancer-targeting peptide p 18-4/chlorin e6 (Ce6)-conjugated polyhedral oligomeric silsesquioxane (PPC) nanoparticles for improving the targeting ability of Ce6 to breast cancer cells, thereby enhancing PDT efficacy. The synthesized PPC nanoparticles exhibited a spherical shape with an average diameter of 127.2 ± 11.3 nm in aqueous solution. Compared with free Ce6, the immobilization of p 18-4 enhanced the in vitro cellular uptake and targeting ability of PPC nanoparticles in breast cancer cell line MDA-MB-231. In addition, the intracellular uptake of PPC nanoparticles in MDA-MB-231 cells was dramatically increased compared with other cancer cells, indicating an obvious targeting ability of PPC nanoparticles on breast cancer cells. Upon light irradiation, PPC nanoparticles revealed significantly improved phototoxicity to MDA-MB-231 cells, mainly due to apoptotic cell death. In vivo PDT study suggested that PPC nanoparticles exhibited increased retention in tumor tissues and effectively inhibited the growth of MDA-MB-231 tumors in a target-specific manner. Overall, these results indicate that PPC nanoparticles are highly effective PDT agents for breast cancer therapy.

Kim YJ ，Lee HI ，Kim JK ，Kim CH ，Kim YJ ... -  《-》

Beta-carotene-bound albumin nanoparticles modified with chlorin e6 for breast tumor ablation based on photodynamic therapy.

Chlorin e6 (Ce6) has attracted considerable interest as a promising second-generation photosensitizer for photodynamic therapy (PDT). However, the in vivo availability of Ce6 is significantly restricted by its low water solubility and poor ability to target tumors. We sought to overcome the limitations of Ce6 by using albumin nanoparticles with nab™ (nanoparticle albumin-bound) technology. The fabricated albumin nanoparticles consisted of bovine serum albumin (BSA), Ce6-BSA, and beta-carotene as a carrier, photosensitizing agent, and cross-linker, respectively. These albumin nanoparticles (Ce6-BSA-BC-NPs) did not include any toxic chemotherapeutics but instead contained naturally safe beta-carotene and Ce6, which was activated only upon irradiation with 660-nm laser light. Ce6-BSA-BC-NPs were ∼120 nm in size and spherical, similar to Abraxane®, and showed good physicochemical stability. The nanoparticles showed significant cytotoxicity toward 4T1 cells as evaluated by MTT, Live/Dead, and TUNEL assays. In particular, results of the TUNEL assay demonstrated that cell death induced by Ce6-BSA-BC-NPs and light irradiation (660 nm) occurred through the apoptotic pathway. Ce6-BSA-BC-NPs displayed a remarkably enhanced tumor suppression effect when irradiated by 660-nm light compared with free Ce6 (tumor volume 90 ± 39 versus 487 ± 69 mm3 respectively). Overall, this improved in vivo antitumor efficacy seemed to be due to the targetability of albumin nanoparticles. We believe that our Ce6-BSA-BC-NPs with PDT offer a promising new potential therapeutic platform for breast cancer treatment.

Phuong PTT ，Lee S ，Lee C ，Seo B ，Park S ，Oh KT ，Lee ES ，Choi HG ，Shin BS ，Youn YS ... -  《-》

Novel carrier-free nanoparticles composed of 7-ethyl-10-hydroxycamptothecin and chlorin e6: Self-assembly mechanism investigation and in vitro/in vivo evaluation.

The combination therapy strategy based on both chemotherapy and photodynamic therapy (PDT) exhibits great potential for advanced cancer treatment. Multimodal nanodrug delivery systems based on both chemotherapeutic drug and photodynamic agent have been proven to possess excellent synergistic efficacy. In this study, 7-ethyl-10-hydroxycamptothecin (SN38) and chlorin e6 (Ce6) were co-assembled into novel carrier-free nanoparticles (SN38/Ce6 NPs) via simple antisolvent precipitation method. As expected, SN38/Ce6 NPs exhibited uniform morphology with a particle size of around 150 nm and a zeta potential of about -30 mV, good stability in aqueous solution/at lyophilized state and high cellular uptake efficiency against murine mammary carcinoma (4T1) cell lines. Besides, enhanced singlet oxygen generation capacity of the nanoparticles was both observed in test-tube and in 4T1 cell lines in contrast with Ce6 injection. Moreover, a ∼85 % inhibition rate of SN38/Ce6 NPs with laser was detected, which was significantly higher (P < 0.05) than those without laser (∼65 %) and injections (less than 20 %), verified the excellent synergistic antitumor efficacy of the nanoparticles due to combined chemo-photodynamic therapy, enhanced tumor accumulation and higher cellular internalization. Notably, chemical thermodynamic method and molecular dynamics (MD) simulations supplied solid data and visual images to estimate the driving forces for the self-assembly process of the carrier-free nanoparticles as primary hydrophobic interactions (π-π stacking) and subordinate hydrogen bonds. Conclusively, the above self-assembled carrier-free nanoparticles represented a promising synergistic anticancer strategy capable of maximal therapeutic efficacy and minimal systemic toxicity. Moreover, the application of thermodynamic method together with MD simulations in the investigation of NPs self-assembly process also provided new ideas for the assembly mechanism exploration of more complicated nanodrug delivery system.

Zhao Y ，Zhao Y ，Ma Q ，Zhang H ，Liu Y ，Hong J ，Ding Z ，Liu M ，Han J ... -  《-》

Boron-based nanosheets for combined cancer photothermal and photodynamic therapy.

Kang Y ，Ji X ，Li Z ，Su Z ，Zhang S ... -  《-》

Chlorin e6 and polydopamine modified gold nanoflowers for combined photothermal and photodynamic therapy.

Wu F ，Liu Y ，Wu Y ，Song D ，Qian J ，Zhu B ... -  《-》