Abstract
Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes) containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed.
Highlights
The complex biology of solid tumors with various biological barriers, e.g., mononuclear-phagocyte system uptake and extravasation through vascular-endothelial layer, and physiological factors, e.g., hypoxia, low pH and raised interstitial-fluid pressure, highlights the need to design and formulate an efficient delivery system for anticancer agents [1]
This study demonstrated the specific targeting of breast cancer cells over-expressing NCL [118]
The liposomes prepared from dipalmitoylphosphatidylcholine (DPPC) and cholesterol released about 80% of encapsulated methotrexate within 0.5 h when the temperature was increased from 37 ◦C to 41 ◦C
Summary
The complex biology of solid tumors with various biological barriers, e.g., mononuclear-phagocyte system uptake and extravasation through vascular-endothelial layer, and physiological factors, e.g., hypoxia, low pH and raised interstitial-fluid pressure, highlights the need to design and formulate an efficient delivery system for anticancer agents [1]. Active targeting with a combination of other approaches, e.g., stimuli sensitivity, is the current approach in tumor therapy In this connection, liposomes are grafted with a variety of targeting ligands, e.g., peptides, aptamers, antibody fragments, etc., using different surface engineering techniques. Liposomes can be engineered for a specific application using suitable surface functionalization and modification techniques, providing the key benefits in cancer therapy of prolonged circulation time, enhanced cellular-uptake, higher payload accumulation at tumor site, by passing lysosomal degradation and stimuli responsive payload release at intended site. Recent approaches for overcoming the current limitations of liposomes and efficient delivery of anticancer agents at tumor site, e.g., functionalization of liposomes with two targeting ligands, modification of liposomes with simultaneous responsiveness to concurrent stimuli and dual functionalized liposomes, responsive to stimuli and grafted with targeting ligands have been reviewed. Challenges and limitations of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed
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