Cancer is a serious challenge to human health, but the current clinical efficacy is far from expected. As the fundamental to improve cancer efficacy is to increase tumor drug concentration and cellular uptake. This article proposes a liposome strategy (GFC) with active targeting, MR-FRET guidance, and multiple stimulus cumulative response capabilities. The liposome can increase the carrier concentration around solid tumors through active targeting and guide exogenous stimulation with magnetic resonance and fluorescence imaging, thereby promoting the dissociation of liposomes through precise, timely, and cumulative stimulation. This strategy highlights the advantages of accumulating multiple stimuli at the same chemical site and the spontaneous membrane fusion characteristics of the incompletely dissociated liposomes. In general, the targeted aggregation D@GFC liposomes can be dissociated most effectively, and according to the dissociation state of the liposomes, it can optimize the cell uptake scheme by active endocytosis, spontaneous membrane fusion, and drug diffusion. Herein, by gradually increasing the stimulus intensity, the pH-based photodissociation ability of the co-assembled GFC liposomes was first verified by UV and fluorescence spectroscopy. Secondly, combining DLS, TEM, and CLSM, we speculate that liposomes may have dissociation-fusion-recombination-fragmentation behavior during dissociation. Subsequently, cytotoxicity, CLSM, and flow cytometric analysis verified that GFC liposomes could fuse with cell membranes after triggering the dissociation state. In vivo and in vitro imaging of mice showed that the relaxation time of GFC liposomes was 3.08 times higher than that of Gd-DTPA, and the tumor had the highest liposome aggregation after 180 min of injection, which verified the targeting ability and the MR-FRET imaging capabilities of GFC liposomes. In addition, tumor treatment experiments show that the tumors of the D@GFC UV group are 9.13 times smaller than those of the PBS group, which has the best inhibitory effect and again emphasizes the advantages of targeted, visual guidance, and cumulative stimulation strategies.

Strategies to improve cell absorption rate: Precise targeting, dual visualization guided, multiple stimulus responsive liposomes for cancer treatment

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.