ABSTRACT
OBJECTIVE@#Bufalin is an effective drug for the treatment of liver cancer. But its high toxicity, poor water-solubility, fast metabolism and short elimination half-life limit its use in tumor treatment. How to make the drug accumulate in the tumor and reduce side effects while maintaining its efficacy are urgent problems to be solved. The goal of this study is to solve these problems.@*METHODS@#A copolymer with tunable poly-N-isopropylacrylamide and polylactic acid was designed and synthesized. The corresponding dual targeting immunomicelles (DTIs) loaded with bufalin (DTIs-BF) were synthesized by copolymer self-assembly in an aqueous solution. The size and structure of DTIs-BF were determined by ZetaSizer Nano-ZS and transmission electron microscopy. Then, its temperature sensitivity, serum stability, critical micelle concentration (CMC), entrapment efficiency (EE), drug release and non-cytotoxicity of blank block copolymer micelles (BCMs) were evaluated. Next, the effects of DTIs-BF on cellular uptake, cytotoxicity, and tumor cell inhibition were evaluated. Finally, the accumulation of DTIs-fluorescein isothiocyanate (FITC) and the in vivo anti-tumor effect were observed using an interactive video information system.@*RESULTS@#DTIs-BF had a small size, spherical shape, good temperature sensitivity, high serum stability, low CMC, high EE, and slow drug release. The blank BCMs had very low cytotoxicity. Compared with free bufalin, the in vitro cellular internalization and cytotoxicity of DTIs-BF against SMMC-7721 cells were significantly enhanced, and the effects were obviously better at 40 °C than 37 °C. In addition, the therapeutic effect on SMMC-7721 cells was further enhanced by the programmed cell death specifically caused by bufalin. When DTIs-FITC were injected intravenously in BALB/c nude mice bearing liver cancer, the accumulation of FITC was significantly increased in tumors.@*CONCLUSION@#DTIs-BF is a potentially effective nano-formulation and has broad prospects in the clinical treatment of liver cancer.
Subject(s)
Animals , Mice , Antineoplastic Agents/pharmacology , Bufanolides , Cell Line, Tumor , Liver Neoplasms/drug therapy , Mice, Inbred BALB C , Mice, NudeABSTRACT
Precision medicine has shown a new hope for cancer treatment because it can provide clear individual disease causes, precision therapeutic targets and accurate classification based on the genome sequencing, bioinformatics, and large database. However, the effective precision therapy should also include how to deliver and release drugs with controlled dosage at the precision therapeutic targets. A challenge in clinical anti-tumor precision therapy is how to achieve precision delivery and regulate the dosage of screened drugs, including how to overcome the biological barrier, how to safely deliver the drugs to nidus, how to enhance intratumoral accumulation of drugs, how to promote endocytosis of target cells, and how to accurately deliver drugs to intracellular therapeutic targets. Nanomedicine can effectively solve the problems as mentioned above. Through fine design and nanocarrier tailoring, nano-products will accurately and efficiently deliver the screened drug molecules to target organs, target tissues, target cells or intracellular target organelles, and precisely release the drug to a desirable dosage under the stimulation of lesions. The combination of precision medicine and nanomedicine can efficiently achieve precision therapy: from the tumor molecular classification, drug screening, drug precision delivery, controlled drug release to the treatment. Consequently, precision medicine mainly refers to accurate diagnosis and accurate screening of drug targets, which is the so called “advance troops and scouts” of precision treatment of cancer. Nanomedicine mainly focuss on the accurate delivery and controlled release of drugs to the therapeutic target, which can be called “accurate strategic bombing”. Both precision medicine and nanomedicine are essential and interdependent elements in precision therapy.