Small Molecular Theranostic Assemblies
Functionalized by Doxorubicin–Hyaluronic Acid–Methotrexate
Prodrug for Multiple Tumor Targeting and Imaging-Guided Combined Chemo-Photothermal
Therapy
posted on 2019-04-17, 00:00authored byYilin Chen, Qing Chen, Qixin Zhu, Jinxue Liu, Yang Li, Xuemin Gao, Dengyue Chen, Xuan Zhu
Because
of high drug payload and minimized burden of foreign materials in
the course of metabolism and excretion, carrier-free nanomedicine
based on self-assembly of small-molecule therapeutic agents has attracted
considerable attention in cancer therapy. However, obstacles still
remained, such as lack of targeting efficiency, poor physiological
stability, and serious drug burst release. Herein, we developed a
self-dual-targeting prodrug conjugate by coupling methotrexate (MTX)
and doxorubicin (DOX) to a hyaluronic acid (HA) backbone which enveloped
the small molecular drug coassemblies of DOX and indocyanine green
for specific targeting and imaging-guided chemo-photothermal therapy
(PTT). The constructed nanosystems exhibited a diameter of ∼200
nm, superior physiological stability, and improved photothermal effect.
Taking advantage of functionality of MTX–HA–DOX conjugate,
the nanosystems remarkably enhanced the accumulation in the tumor
regions by enhanced penetration and retention effect and CD44/folate receptor-mediated endocytosis. Upon the stimuli of acid,
the nanosystems showed the rapid disassembly followed by the accelerated
drug release. Consequently, the nanosystems demonstrated highly efficient
apoptosis in cancer cells and remarkable tumor ablation by synergy
between chemotherapy and PTT upon the irradiation of near-infrared
laser. The multifunctional nanosystems based on small molecular theranostic
assemblies could provide a promising potential in developing dual-targeting
drug delivery and imaging-guided combinational therapy.