A pH-responsive α-helical cell penetrating peptide-mediated liposomal delivery system.

摘要: Tumor-oriented nanocarrier drug delivery approaches with pH-sensitivity have been drawing considerable attentions over the years. Here we described a liposomal system modified pH-responsive cell penetrating peptide TH (TH-Lip). Conventional (CPP)-related tactics sometimes seemed limited due to extensive in vivo penetration and lack of proper selectivity conventional CPPs. In this study, (AGYLLGHINLHHLAHL(Aib)HHIL-NH2), an engineered α-helical originated from TK (AGYLLGKINLKKLAKL(Aib)LLIL-NH2), was endowed pH-responsiveness after complete replacement all lysines sequence into histidines, introduced onto surface liposomes. Accordingly, TH-Lip could benefit unique property TH, as capacity concealed during blood circulation normal tissues because neutral pH under those conditions. However, when reached tumor, declined, histidines protonated charge converted negative positive, initiating activated leading enhanced cellular tumor spheroid uptake. The endocytosis inhibition assay demonstrated that influenced by positively charged liposomes acidic environment mediated clathrin, intracellular trafficking study suggested were mainly accumulated endoplasmic reticulum Golgi apparatus. After systemic administration mice, be internalized cells efficaciously. When it comes paclitaxel (PTX), led strong against growth which occurred both vitro (under 6.3) vivo, rate 86.3% on C26 tumor-bearing mice for PTX-loaded TH-Lip. Therefore, proved itself promising strategy within acidified microenvironment.