Near-Infrared Cyanine-Loaded Liposome-like Nanocapsules of Camptothecin–Floxuridine Conjugate for Enhanced Chemophotothermal Combination Cancer Therapy

Abstract

A dual-in-dual synergistic strategy was proposed based on the self-assembly of combinatorial nanocapsules (NCs) from Janus camptothecin-floxuridine (CF) conjugate and the near-infrared absorber of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR) by introducing PEGylated phospholipid of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycerol)-2000] to increase the blood circulation time of NCs. Due to the use of amphiphilic CF and DiR themselves to form liposome-like nanocapsules, the obtained CF-DiR NCs owned a significantly high loading content, a stable co-delivery drug combinations, a no premature release, and an excellent photothermal conversion efficiency. The in vivo fluorescence imaging indicated that CF-DiR NCs could achieve a high tumor accumulation after an intravenous injection. The dual drugs of camptothecin and floxuridine could be coordinately released due to the hydrolysis of the ester bond by the esterase in tumor. The in vivo experiments showed that more cytotoxicity of the CF-DiR NCs-mediated chemo- and photothermal dual therapy to tumor cells could be clearly observed than the chemotherapy or photothermal therapy alone due to the synergistic effect, leading to no recurrence in the entire treatment. All of the results highlighted that CF-DiR NCs were highly effective theranostic agents that could be used for imaging-guided cancer chemophotothermal therapy to conquer an intrinsic resistance to chemotherapeutics.

Ultrasound contrast agent microbubbles with ultrahigh loading capacity of camptothecin and floxuridine for enhancing tumor accumulation and combined chemotherapeutic efficacy

“…It has been reported that anticancer drug combinations simultaneously delivered to tumor cells can afford synergistic therapeutic effects, thus overcoming tumor heterogeneity and drug resistance issues. The combination of irinotecan and a fluoropyrimidine derivative in a synergistic 1:1 molar ratio inside a liposome has been demonstrated to provide greatly enhanced antitumor therapeutic efficacy [30][31][32][33][34] . In this study, a highly symmetric Janus camptothecinfloxuridine (CF) conjugate linked with two hydrophobic camptothecin (CPT) molecules and two hydrophilic floxuridine (FUDR) molecules and with multivalent pentaerythritol through hydrolyzable ester bonds was synthesized using a protection-deprotection strategy [33][34][35] .…”

“…The combination of irinotecan and a fluoropyrimidine derivative in a synergistic 1:1 molar ratio inside a liposome has been demonstrated to provide greatly enhanced antitumor therapeutic efficacy [30][31][32][33][34] . In this study, a highly symmetric Janus camptothecinfloxuridine (CF) conjugate linked with two hydrophobic camptothecin (CPT) molecules and two hydrophilic floxuridine (FUDR) molecules and with multivalent pentaerythritol through hydrolyzable ester bonds was synthesized using a protection-deprotection strategy [33][34][35] . Its amphiphilic structure facilitates the self-assembly of CF MBs, enabling highly stable codelivery of drug combinations from conjugates with remarkably high drug-loading content (DLC), a fixed CPT/FUDR molar ratio of 1:1 and no premature release (Scheme 1).…”

Self‐Assembled Supramolecular Nanoparticles for Targeted Delivery and Combination Chemotherapy

“…The combination index (CI) is used to evaluate the synergistic effect of combination therapies. If CI<1, it suggests that different drugs act synergistically; otherwise, that is, if CI=1 or CI>1, the drugs act additively or antagonistically …”

“…If CI < 1, it suggestst hat different drugs act synergistically;o therwise, that is, if CI = 1o rC I> 1, the drugs act additively or antagonistically. [38,39] To evaluate the influence of poly-b-CD on the experimental results, we investigated its potential toxicity.T he blank sample of poly-b-CD was incubated with CCRF-CEMa nd Ramos (human Burkitt lymphoma) cell lines for 48 h. With use of a standard MTS assay, the cell viability of cells remained above 80 %, demonstrating that the carrierh ad little cytotoxicity toward these cell lines within ac ertain concentration range ( Figure 3A).…”

A multifunctional biodegradable brush polymer-drug conjugate for paclitaxel/gemcitabine co-delivery and tumor imaging

“…The integration of co-delivered anticancer drugs with cancer imaging agents is an approach that could be of interest. [41][42][43][44][45] However, integrated systems demonstrating PTX/GEM codelivery with cancer imaging agents have not yet been reported.…”