Recent trends in multifunctional liposomal nanocarriers for enhanced tumor targeting

Abstract

Liposomes are delivery systems that have been used to formulate a vast variety of therapeutic and imaging agents for the past several decades. They have significant advantages over their free forms in terms of pharmacokinetics, sensitivity for cancer diagnosis and therapeutic efficacy. The multifactorial nature of cancer and the complex physiology of the tumor microenvironment require the development of multifunctional nanocarriers. Multifunctional liposomal nanocarriers should combine long blood circulation to improve pharmacokinetics of the loaded agent and selective distribution to the tumor lesion relative to healthy tissues, remote-controlled or tumor stimuli-sensitive extravasation from blood at the tumor's vicinity, internalization motifs to move from tumor bounds and/or tumor intercellular space to the cytoplasm of cancer cells for effective tumor cell killing. This review will focus on current strategies used for cancer detection and therapy using liposomes with special attention to combination therapies.

Figure 1

Schematic picture of a multifunctional liposomal nanocarrier.

Figure 2

Schemes for tumor-specific liposome destabilization or endocytosis.

Figure 3

Targeting mechanisms in liposomal cancer therapy.

Figure 4

Strategies for intracellular delivery. Steps for intracellular delivery: (1) Stimuli-sensitive activation/unmasking of internalization moiety, (2) Cancer cell-specific endocytosis, (3) Endosomal escape and/or therapeutic agent release after activation of fusogenic peptides or lipids, (4) Binding to the highly negative mitochondrial outer membrane for mitochondria targeting. Legends are the same as in Figure 1.