Dual Chemodrug-Loaded Single-Walled Carbon Nanohorns for Multimodal Imaging-Guided Chemo-Photothermal Therapy of Tumors and Lung Metastases

Abstract

Tumor combination therapy using nano formulations with multimodal synergistic therapeutic effects shows great potential for complete ablation of tumors. However, targeting tumor metastases with nano structures is a major obstacle for therapy. Therefore, developing a combination therapy system able to target both primary tumors and their metastases at distant sites with synergistic therapy is desirable for the complete eradication of tumors. To this end, a dual chemodrug-loaded theranostic system based on single walled carbon nanohorns (SWNHs) is developed for targeting both primary breast tumors and their lung metastases.Methods: SWNHs were first modified simultaneously with poly (maleic anhydride-alt-1-octadecene) (C18PMH) and methoxypolyethyleneglycol-b-poly-D, L-lactide (mPEG-PLA) via hydrophobic-hydrophobic interactions and π-π stacking. Then cisplatin and doxorubicin (DOX) (2.9:1 molar ratio) were sequentially loaded onto the modified nanohorns in a noninterfering way. After careful examinations of the release profiles of the loaded drugs and the photothermal performance of the dual chemodrug-loaded SWNHs, termed SWNHs/C18PMH/mPEG-PLA-DOX-Pt, the dual drug chemotherapeutic and chemo-photothermal synergetic therapeutic effects on tumor cells were evaluated. Subsequently, the in vivo behavior and tumor accumulation of the drug-loaded SWNHs were studied by photoacoustic imaging (PAI). For chemo-photothermal therapy of tumors, 4T1 tumor bearing mice were intravenously injected with SWNHs/C18PMH/mPEG-PLA-DOX-Pt at a dose of 10 mg/kg b.w. (in SWNHs) and tumors were illuminated by an 808 nm laser (1W/cm2 for 5 min) 24 h post-injection.Results: DOX and cisplatin were loaded onto the modified SWNHs with high efficiency (44 wt% and 66 wt%, respectively) and released in a pH-sensitive, tandem and sustainable manner. The SWNHs/C18PMH/mPEG-PLA-DOX-Pt had a hydrodynamic diameter of 182 ± 3.2 nm, were highly stable in physiological environment, and had both dual drug chemotherapeutic (CI = 0.439) and chemo-photothermal synergistic antitumor effects (CI = 0.396) in vitro. Moreover, the dual drug-loaded SWNHs had a long blood half-life (10.9 h) and could address both the primary breast tumors and their lung metastases after intravenous administration. Consequently, chemo-photothermal combination therapy ablated the primary tumors and simultaneously eradicated the metastatic lung nodules.Conclusion: Our study demonstrates that SWNHs/C18PMH/mPEG-PLA-DOX-Pt is highly potent for chemo-photothermal combination therapy of primary tumors and cocktail chemotherapy of their metastases at a distant site.

Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer

“…In another study, Zhang and co-authors simultaneously loaded Dox and cisplatin onto polymer modified single walled carbon nanohorns (SWNHs) as a chemo-photothermal theranostic system. 352 Both synergistic effect of Dox and cisplatin and chemotherapy and PTT improved in vitro treatment of 4T1 cancer cells. In vivo study showed that combination of PTT and chemotherapy had the best treatment outcomes.…”

“…Combining PTT and chemotherapy can generate improved treatment outcomes. [351][352][353][354][355] In this context, Chen and co-workers developed the supramolecular micelles assembled from polyrotaxane building blocks as a theranostic platform. 351 The axle of polyrotaxane was amphiphilic PDI terminated block copolymer of PEG-b-poly(ε-caprolactone) (PCL), which formed hostguest complexation with the wheel of the primary-amino-containing β-cyclodextrin (β-CD-NH 2 ).…”

Carbon fibers for treatment of cancer metastasis in bone

“…As such, the sustained release speed has been reported to vary depending on carbon material surface structure or ambient pH. [27][28][29][30] Although anticancer agent release can be slowed by regulating carbon nanober surface structure and ambient pH, this approach remains to be investigated in the future.…”

Single-Walled Carbon Nanohorns as Promising Nanotube-Derived Delivery Systems to Treat Cancer

“…The attachment of polymers such as amphiphilic lipid-based poly (ethylene glycol) has also been suggested to produce water-stable SWCNH through non-covalent functionalization [ 40 ]. Similarly, another recent study has proposed to modify SWCNHs with poly (maleic anhydride- alt -1-octadecene) and methoxypolyethylene glycol-b-poly( d , l -lactide), to sequentially load different drugs for combined chemo-photothermic therapy [ 41 ]. Other authors have used a block polyelectrolyte wrapping strategy for the development of a soluble nanohybrid, stable for several months.…”