TY - JOUR
T1 - Super-small zwitterionic micelles enable the improvement of blood-brain barrier crossing for efficient orthotopic glioblastoma combinational therapy
AU - Wang, Ke
AU - Zhao, Bingbing
AU - Ao, Yuli
AU - Zhu, Jinyu
AU - Zhao, Changshun
AU - Wang, Wei
AU - Zou, Yan
AU - Huang, Dechun
AU - Zhong, Yinan
AU - Chen, Wei
AU - Qian, Hongliang
PY - 2023/12
Y1 - 2023/12
N2 - Glioblastoma multiforme (GBM) remains incurable in clinical, nanotechnology-based drug delivery strategies show promising perspective in alleviating GBM, while limited blood-brain-barrier (BBB) permeation, short blood half-live accompanied by the poor tumor accumulation and penetration, significantly restrict the therapeutic outcomes. Herein, a versatile super-small zwitterionic nano-system (MCB(S)) based on carboxybetaine (CB) zwitterion functionalized hyperbranched polycarbonate (HPCB) is developed to overcome the brain delivery challenges. After grafting with amino-functionalized IR780 (free IR780), the ultimate paclitaxel (PTX)-encapsulated micelles (MCB(S)-IR@PTX) are precisely activated by near-infrared (NIR) for accelerated drug release and effective combinational GBM therapy. Importantly, MCB(S)-IR@PTX with the crosslinked structure and CB zwitterion prolongs blood-circulation, and CB-zwitterion further facilitates BBB-traversing through betaine/γ-aminobutyric acid (GABA) transporter-1 (BGT-1) pathway. Combined with the benefit of super small-size, MCB(S)-IR@PTX highly accumulates at tumor sites and penetrates deeply, thus efficiently inhibiting tumor growth and strikingly improving survival time in U87MG orthotopic GBM-bearing mouse model. The ingenious nanoplatform furnishes a versatile strategy for delivering therapeutics into the brain and realizing efficient brain cancer therapy.
AB - Glioblastoma multiforme (GBM) remains incurable in clinical, nanotechnology-based drug delivery strategies show promising perspective in alleviating GBM, while limited blood-brain-barrier (BBB) permeation, short blood half-live accompanied by the poor tumor accumulation and penetration, significantly restrict the therapeutic outcomes. Herein, a versatile super-small zwitterionic nano-system (MCB(S)) based on carboxybetaine (CB) zwitterion functionalized hyperbranched polycarbonate (HPCB) is developed to overcome the brain delivery challenges. After grafting with amino-functionalized IR780 (free IR780), the ultimate paclitaxel (PTX)-encapsulated micelles (MCB(S)-IR@PTX) are precisely activated by near-infrared (NIR) for accelerated drug release and effective combinational GBM therapy. Importantly, MCB(S)-IR@PTX with the crosslinked structure and CB zwitterion prolongs blood-circulation, and CB-zwitterion further facilitates BBB-traversing through betaine/γ-aminobutyric acid (GABA) transporter-1 (BGT-1) pathway. Combined with the benefit of super small-size, MCB(S)-IR@PTX highly accumulates at tumor sites and penetrates deeply, thus efficiently inhibiting tumor growth and strikingly improving survival time in U87MG orthotopic GBM-bearing mouse model. The ingenious nanoplatform furnishes a versatile strategy for delivering therapeutics into the brain and realizing efficient brain cancer therapy.
KW - Blood-brain-barrier
KW - Combinational therapy
KW - Deep tumor penetration
KW - Prolonged blood circulation
KW - Super-small zwitterionic micelle
UR - http://www.scopus.com/inward/record.url?scp=85175352943&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2023.10.019
DO - 10.1016/j.jconrel.2023.10.019
M3 - Article
C2 - 37839641
AN - SCOPUS:85175352943
SN - 0168-3659
VL - 364
SP - 261
EP - 271
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -