Abstract
The therapeutic index of chemotherapeutic agents can be improved by the use of nano-carrier-mediated chemotherapeutic delivery. Ligand-targeted drug delivery can be used to achieve selective and specific delivery of chemotherapeutic agents to cancer cells. In this study, we prepared a peptidomimetic conjugate (SA-5)-tagged doxorubicin (Dox) incorporated liposome (LP) formulation (SA-5-Dox-LP) to evaluate the targeted delivery potential of SA-5 in human epidermal growth factor receptor-2 (HER2) overexpressed non-small-cell lung cancer (NSCLC) and breast cancer cell lines. The liposome was prepared using thin lipid film hydration and was characterized for particle size, encapsulation efficiency, cell viability, and targeted cellular uptake. In vivo evaluation of the liposomal formulation was performed in a mice model of NSCLC. The cell viability studies revealed that targeted SA-5-Dox-LP showed better antiproliferative activity than non-targeted Dox liposomes (Dox-LP). HER2-targeted liposome delivery showed selective cellular uptake compared to non-targeted liposomes on cancer cells. In vitro drug release studies indicated that Dox was released slowly from the formulations over 24 h, and there was no difference in Dox release between Dox-LP formulation and SA-5-Dox-LP formulation. In vivo studies in an NSCLC model of mice indicated that SA-5-Dox-LP could reduce the lung tumors significantly compared to vehicle control and Dox. In conclusion, this study demonstrated that the SA-5-Dox-LP liposome has the potential to increase therapeutic efficiency and targeted delivery of Dox in HER2 overexpressing cancer.
Highlights
The major drawback associated with currently available chemotherapeutics is the lack of targeted delivery toward cancer cells
We showed that showed that stearic acid (SA)‐5 exhibited better selectivity for human epidermal growth factor receptor-2 (HER2) (EGFR) overexpressed cancer cellsSA-5 exhibited for HER2 (EGFR)
We have successfully developed a peptidomimetic-tagged liposome containing Dox that can effectively target HER2 overexpressed breast and lung cancer cells
Summary
The major drawback associated with currently available chemotherapeutics is the lack of targeted delivery toward cancer cells. This non-selective effect leads to increased toxicity to healthy cells [1,2]. The therapeutic index of chemotherapeutic agents can be improved by the use of nano-carrier-mediated chemotherapeutic delivery. Nano-carriermediated chemotherapeutic delivery has been shown to maximize the therapeutic index and decrease toxicity toward normal cells [2]. The use of nano-carrier liposomes is known to be a successful strategy for increasing the delivery of anti-cancer drugs to tumors [3]. Polyethylene glycol (PEGylated)-incorporated liposomes are stealth liposomes that offer improved half-life of a formulation in vivo.
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