ABSTRACT
Charge-reversal nanocarrier was constructed to enhance lysosomal escape and improve an-titumor effect. We synthesized the cholesterol-polyethyleneimine-hexahydrophthalic anhydride (Chol-PEI-HHPA) polymer and characterized by 1H NMR. The charge-reversal liposomes (Lipo-HHPA) were synthesized and the hematoporphyrin monomethyl ether (HMME) was loaded. pH-triggered charge conversion was determined at different pH values. The lysosomal escape and cytotoxicity of the Lipo-HHPA were evaluated in MCF-7 cells. The Lipo-HHPA was uniform with an average particle size of 102 nm. Upon the irradiation of ultrasound, burst release of HMME could be observed. The zeta potential of Lipo-HHPA changed sharply from negative (-23.5 mV) to positive (+21.2 mV) over the pH range of 7.4-4.5. In the cellular uptake experiment, the lysosomal escape of Lipo-HHPA was observed. HMME loaded Lipo-HHPA displayed obviously enhanced cytotoxicity towards MCF-7 cells. These results indicate that the charge-reversal liposomes hold a great potential in improving the cytotoxicity and antitumor effect.
ABSTRACT
OBJECTIVE: To synthesize the biomacromolecule of poly-malic acid (PMLA) for preparation of a novel 2,3-dimeth-ylmaleic anhydride-decorated polyethyleneimine-pory(β-L-malic acid)-doxorubicin nanoconjugate for effective and specific drug delivery. METHODS: The structures of PMLA and the nanoconjugate were confirmed by 1H-NMR. Then the conjugation efficiency and drug release property were determined. The cellular uptake and cytotoxicity were assessed by using human hepatocellular carcinoma (HCC) cell line Huh7 as in vitro cell model. RESULTS: PMLA and DOX/PMLA-PEI-DMA were successfully prepared. The nanoconjugate possessed pH-sensitive charge-conversion and pH-dependent drug release properties. DOX/PMLA-PEI-DMA enhanced the cellular uptake of DOX and in vitro cytotoxicity effectively. CONCLUSION: Nanoconjugate DOX/PMLA-PEI-DMA can be used as a promising drug carrier for its targeted and intracellular delivery.