Stimulus-responsive nanopreparations for tumor targeting

Abstract

Nanopreparations such as liposomes, micelles, polymeric and inorganic nanoparticles, and small molecule/nucleic acid/protein conjugates have demonstrated various advantages over "naked" therapeutic molecules. These nanopreparations can be further engineered with functional moieties to improve their performance in terms of circulation longevity, targetability, enhanced intracellular penetration, carrier-mediated enhanced visualization, and stimuli-sensitivity. The idea of application of a stimulus-sensitive drug or imaging agent delivery system for tumor targeting is based on the significant abnormalities in the tumor microenvironment and its cells, such as an acidic pH, altered redox potential, up-regulated proteins and hyperthermia. These internal conditions as well as external stimuli, such as magnetic field, ultrasound and light, can be used to modify the behavior of the nanopreparations that control drug release, improve drug internalization, control the intracellular drug fate and even allow for certain physical interactions, resulting in an enhanced tumor targeting and antitumor effect. This article provides a critical view of current stimulus-sensitive drug delivery strategies and possible future directions in tumor targeting with primary focus on the combined use of stimulus-sensitivity with other strategies in the same nanopreparation, including multifunctional nanopreparations and theranostics.

Figure 1

Stimulus-responsive delivery strategies for tumor targeting.

Figure 2

Schematic representation of pH-sensitive DMAEMA/HEMA nanoparticle-mediated gene transfection with and without bafilomycin A1 as a V ATPase inhibitor (Reproduced with permission from ref.).

Figure 3

Cytotoxicity of PEI (125KDa and 1800Da) and PEI(1800)-PE in B16F10 cells (A) ( Reproduced with permission from ref. ); Cellular uptake of DNA from different complexes [PEI(1800) N/P 16, PEI (25K)N/P 4, PEI(1800) -PE N/P 16] in B16F10 cells after 4h (B) ( Reproduced with permission from ref. ); GFP down-regulation by GFP siRNA/PEI (1800) (C) and siRNA/PEI(1800)-PE (D) in C166-GFP cells (Reproduced with permission from ref.).

Figure 4

Synthesis scheme (A) and siRNA release (B) of Gal-PEG-siRNA and M6P-PEG-siRNA (Reproduced with permission from ref.).

Figure 5

Enhanced tumor targeting using a MMP2-responsive liposomal multifunctional nanocarrier. Reproduced with permission from ref..