TY - JOUR
T1 - Dual-functional liposomes with carbonic anhydrase IX antibody and BR2 peptide modification effectively improve intracellular delivery of cantharidin to treat orthotopic hepatocellular carcinoma mice
AU - Zhang, Xue
AU - Lin, Congcong
AU - Chan, Waikei
AU - Liu, Kanglun
AU - LYU, Aiping
AU - Lin, Ge
AU - Hu, Rong
AU - Shi, Hongcan
AU - ZHANG, Hong Qi
AU - YANG, Zhijun
N1 - Funding Information:
Funding: This work was supported by the University Grants Committee of Hong Kong for the General Research Fund (HKBU 12102514) and the Hong Kong Baptist University Faculty Research Grant (FRG2/14-15/082).
PY - 2019/9/12
Y1 - 2019/9/12
N2 - Liposomal nanotechnology has a great potential to overcome the current major problems of chemotherapy. However, the lack of penetrability and targetability retards the successful delivery of liposomal carriers. Previously, we showed that BR2 peptide modification endowed cantharidin-loaded liposomes with intracellular penetration that enhanced the drug cytotoxic effects. Here, we aimed to improve the targeting delivery of drugs into cancer cells via highly expressed carbonic anhydrase IX (CA IX) receptors by modifying our previous catharidin-loaded BR2-liposomes with anti-CA IX antibody. A higher cellular uptake of dual-functional liposomes (DF-Lp) than other treatments was observed. Induction of CA IX over-expressing resulted in a higher cellular binding of DF-Lp; subsequently, blocking with excess antibodies resulted in a decreased cancer-cell association, indicating a specific targeting property of our liposomes towards CA IX expressed cells. After 3h tracking, most of the liposomes were located around the nucleus which confirmed the involvement of targeting intracellular delivery. Cantharidin loaded DF-Lp exhibited enhanced cytotoxicity in vitro and was most effective in controlling tumor growth in vivo in an orthotopic hepatocellular carcinoma model compared to other groups. Collectively, our results presented the advantage of the BR2 peptide and CA IX antibody combination to elevate the therapeutic potential of cantharidin loaded DF-liposomes.
AB - Liposomal nanotechnology has a great potential to overcome the current major problems of chemotherapy. However, the lack of penetrability and targetability retards the successful delivery of liposomal carriers. Previously, we showed that BR2 peptide modification endowed cantharidin-loaded liposomes with intracellular penetration that enhanced the drug cytotoxic effects. Here, we aimed to improve the targeting delivery of drugs into cancer cells via highly expressed carbonic anhydrase IX (CA IX) receptors by modifying our previous catharidin-loaded BR2-liposomes with anti-CA IX antibody. A higher cellular uptake of dual-functional liposomes (DF-Lp) than other treatments was observed. Induction of CA IX over-expressing resulted in a higher cellular binding of DF-Lp; subsequently, blocking with excess antibodies resulted in a decreased cancer-cell association, indicating a specific targeting property of our liposomes towards CA IX expressed cells. After 3h tracking, most of the liposomes were located around the nucleus which confirmed the involvement of targeting intracellular delivery. Cantharidin loaded DF-Lp exhibited enhanced cytotoxicity in vitro and was most effective in controlling tumor growth in vivo in an orthotopic hepatocellular carcinoma model compared to other groups. Collectively, our results presented the advantage of the BR2 peptide and CA IX antibody combination to elevate the therapeutic potential of cantharidin loaded DF-liposomes.
KW - BR2 peptide
KW - Cantharidin
KW - Carbonic anhydrase IX
KW - Dual-functionalized liposomes
KW - Hepatocellular carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85072223668&partnerID=8YFLogxK
U2 - 10.3390/molecules24183332
DO - 10.3390/molecules24183332
M3 - Journal article
C2 - 31547459
AN - SCOPUS:85072223668
SN - 1420-3049
VL - 24
JO - Molecules
JF - Molecules
IS - 18
M1 - 3332
ER -
