1 research outputs found
Methotrexate–Camptothecin Prodrug Nanoassemblies as a Versatile Nanoplatform for Biomodal Imaging-Guided Self-Active Targeted and Synergistic Chemotherapy
“All-in-one”
carrier-free-based nano-multi-drug self-delivery system could combine
triple advantages of small molecules, nanoscale characteristics, and
synergistic combination therapy together. Researches have showed that
dual-acting small-molecular methotrexate (MTX) could target and kill
the folate-receptor-overexpressing cancer cells. Inspired by this
mechanism, a novel collaborative early-phase tumor-selective targeting
and late-phase synergistic anticancer approach was developed for the
self-assembly of chemotherapeutic drug–drug conjugate, which
showed various advantages of more simplicity, efficiency, and flexibility
over the conventional approach based only on single or combination
cancer chemotherapy. MTX and 10-hydroxyl camptothecin (CPT) were chosen
to conjugate through ester linkage. Because of the amphiphilicity
and ionicity, MTX-CPT conjugates as molecular building blocks could
self-assemble into MTX-CPT nanoparticles (MTX-CPT NPs) in aqueous
solution, thus notably improving the aqueous solubility of CPT and
the membrane permeability of MTX. The MTX-CPT NPs with a precise drug-to-drug
ratio showed pH-/esterase-responsive drug release, sequential function “Targeting–Anticancer”
switch, and real-time monitoring fluorescence “Off–On”
switch. By doping with a lipophilic near-infrared (NIR) cyanine dye
(e.g., 1′-dioctadecyl-3,3,3′,3′-tetramethylindoÂtricarbocyanine
iodide, DiR), the prepared DiR-loaded MTX-CPT NPs acted as an effective
probe for <i>in vivo</i> NIR fluorescence (NIRF) and photoacoustic
(PA) dual-modal imaging. Both <i>in vitro</i> and <i>in vivo</i> studies demonstrated that MTX-CPT NPs could specifically
codeliver multidrug to different sites of action with distinct anticancer
mechanisms to kill folate-receptor-overexpressing tumor cells in a
synergistic way. This novel, simple, and highly convergent self-targeting
nanomulti-drug codelivery system exhibited great potential in cancer
therapy