Dual-Targeting and Stimuli-Triggered Liposomal Drug Delivery in Cancer Treatment

AlSawaftah, N; Pitt, WG; Husseini, GA

Abstract

The delivery of chemotherapeutics to solid tumors using smart drug delivery systems (SDDSs) takes advantage of the unique physiology of tumors (i.e., disordered structure, leaky vasculature, abnormal extracellular matrix (ECM), and limited lymphatic drainage) to deliver anticancer drugs with reduced systemic side effects. Liposomes are the most promising of such SDDSs and have been well investigated for cancer therapy. To improve the specificity, bioavailability, and anticancer efficacy of liposomes at the diseased sites, other strategies such as targeting ligands and stimulus-sensitive liposomes have been developed. This review highlights relevant surface functionalization techniques and stimuli-mediated drug release for enhanced delivery of anticancer agents at tumor sites, with a special focus on dual functionalization and design of multistimuli responsive liposomes.

Keywords: cancer; nanocarrier; targeted delivery; liposomes; active targeting; stimulus

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Liposome System

Stimulus-triggered liposomal drug delivery is a cutting-edge approach in cancer therapy, designed to enhance the precision and efficacy of treatments. Liposomes, which are spherical vesicles composed of lipid bilayers, can encapsulate chemotherapeutic agents, protecting them from degradation and reducing systemic toxicity. These liposomes can be engineered to release their payload in response to specific stimuli present in the tumor microenvironment, such as pH, temperature, or enzymes. For example, pH-sensitive liposomes release drugs in the acidic environment of tumors, ensuring localized drug delivery. Temperature-sensitive liposomes can be triggered by external hyperthermia, concentrating the treatment at the tumor site. Enzyme-sensitive liposomes respond to proteases or other enzymes overexpressed in cancerous tissues, providing another level of specificity. This targeted delivery minimizes damage to healthy tissues and enhances the concentration of drugs within tumors, improving therapeutic outcomes and reducing side effects. Stimulus-triggered liposomal systems represent a significant advancement in the quest for more effective and safer cancer treatments.