Mixiao Tan,Xuemei Li,Hua Zhang,Min Zheng,Jie Xiong,Yang Cao,Guoliang Cao,Zhigang Wang,Haitao Ran
Synergistic photodynamic and photothermal therapy (PDT-PTT) has emerged as an appealing effective antitumor approach. However, clinical utilization of PDT-PTT is plagued by aggregation-caused photobleaching, sequential double irradiations, unsatisfying balance between single oxygen ( 1 O 2 ) quantum yield and photothermal conversion efficiency. Here, an anchored tumor-homing cell-penetrating peptide (PEGA- p VEC) and PANI-ES/HMME loaded FRET nanobullet (AHP-P) are reported. Within nanobullet, HMME (donor) and PANI-ES (acceptor) spontaneously form a förster resonance energy transfer (FRET) pair. Upon 660 nm laser irradiation, HMME convert near-infrared fluorescence (NIRF) to PANI, thus produce FRET-amplified photoacoustic imaging guided PTT. In addition, AHP-P with pH-sensitivity can gradually release HMME within acidic tumor environment, boosts the 1 O 2 regeneration alongside with highly efficient photothermal conversion for photoinduced cancer PTT-PDT. Furthermore, the AHP-P nanobullet can home in on the tumor site and penetrate into cytoplasm through PEGA- p VEC, inducing remarkable tumor regression with an ≈80% tumor volume reduction and decreased skin phototoxicity in vivo during FRET-amplified PTT-PDT.
Drug resistance renders standard chemotherapy ineffective in the treatment of connective tissue growth factor (CTGF)-overexpressing breast cancer. By co-embedding the breast tumor cell-penetrating peptide (PEGA-pVEC) and hyaluronic acid (HA) as a targeting media, novel cascaded targeting nanoparticles (HACT NPs) were created on a rattle mesoporous silica (rmSiO 2 ) scaffold for the pinpoint delivery of siRNAs along with an anticancer drug, aiming at overcoming the drug resistance of CTGF-overexpressing breast cancer in vivo . The targeting nanoparticles selectively accumulated in the vasculature under the guidance of the PEGA-pVEC peptide, cascaded by receptor-mediated endocytosis with the aid of another targeting agent, HA, presenting a greater in vivo tumor targeting ability than single targeting ligand vectors. In addition, an HA shell prevented the leakage of therapeutic drugs during the cargo transport process, until the hyaluronidase (HAase)-triggered degradation upon lysosomes entering, guaranteeing a controllable drug release inside the target cells. When the protective shell disintegrates, the released siRNA took charge to silence the gene associated with drug resistance, CTGF, thus facilitating doxorubicin-induced apoptosis. The cascaded targeting media (PEGA-pVEC and HA) advances precision-guided therapy in vivo , while the encapsulation of siRNAs into a chemotherapy drug delivery system provides an efficient strategy for the treatment of drug resistance cancers.
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