Dual-self-recognizing, stimulus-responsive and carrier-free methotrexate–mannose conjugate nanoparticles with highly synergistic chemotherapeutic effects

Fan, Zhongxiong; Wang, Yinqiang; Xiang, Sijin; Zuo, Wenbao; Huang, Doudou; Jiang, Beili; Yin, Wen; Xie, Liping; Hou, Zhenqing

doi:10.1039/d0tb00049c

Cited by 31 publications

(17 citation statements)

References 36 publications

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“…Notably, although no surfactants, excipients, or stabilizers were introduced, PFP still possessed a favorable physiological stability without remarkable aggregation or phase separation in PBS, RPMI 1640, and RPMI 1640 containing 10% FBS in 7 d, implying that PFP could be expected to maintain an intact nanostructure during blood circulation, circumvent the reticular endothelial system (RES) uptake, and then accumulate at tumor areas. 43 These experimental phenomena combined with previous studies disclosed that the metal−organic supramolecular scaffolds played a critical role in PFP stability, indicating that coordination-driven supramolecular sequential co-assembly of PAB, PEM, and Fe III efficiently elevated the dispersity, integrality, stability, and drug payload rate of PFP. 16,23,44 2.3.…”

Section: Resultssupporting

confidence: 57%

Trojan-Horse Diameter-Reducible Nanotheranostics for Macroscopic/Microscopic Imaging-Monitored Chemo-Antiangiogenic Therapy

Fan

Shi

Zuo

et al. 2022

ACS Appl. Mater. Interfaces

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Although nanotheranostics have displayed striking potential toward precise nanomedicine, their targeting delivery and tumor penetration capacities are still impeded by several biological barriers. Besides, the current antitumor strategies mainly focus on killing tumor cells rather than antiangiogenesis. Enlightened by the fact that the smart transformable self-targeting nanotheranostics can enhance their targeting efficiency, tumor penetration, and cellular uptake, we herein report carrier-free Trojan-horse diameter-reducible metal−organic nanotheranostics by the coordination-driven supramolecular sequential co-assembly of the chemodrug pemetrexed (PEM), transition-metal ions (Fe III ), and antiangiogenesis pseudolaric acid B. Such nanotheranostics with both a high dual-drug payload efficiency and outstanding physiological stability are responsively decomposed into numerous ultra-small-diameter nanotheranostics under stimuli of the moderate acidic tumor microenvironment and then internalized into tumor cells through tumor-receptor-mediated self-targeting, synergistically enhancing tumor penetration and cellular uptake. Besides, such nanotheranostics enable visualization of self-targeting capacity under the macroscopic monitor of computed tomography/magnetic resonance imaging, thereby realizing efficient oncotherapy. Moreover, tumor microvessels are precisely monitored by optical coherence tomography angiography/laser speckle imaging during chemo-antiangiogenic therapy in vivo, visually verifying that such nanotheranostics possess an excellent antiangiogenic effect. Our work will provide a promising strategy for further tumor diagnosis and targeted therapy.

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Section: Resultssupporting

confidence: 57%

Trojan-Horse Diameter-Reducible Nanotheranostics for Macroscopic/Microscopic Imaging-Monitored Chemo-Antiangiogenic Therapy

Fan

Shi

Zuo

et al. 2022

ACS Appl. Mater. Interfaces

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“…To achieve the combined enhanced chemoradiation therapy of the two drugs, namely MTX as the chemotherapeutic and targeting agent and CUR as a natural radioprotector that improves chemotherapy and reduces side effects, they were both loaded into the nanoparticles [ 35 , 36 ]. To confirm the chemical composition of the hybrid nanostructures, Uv–Vis and FTIR spectra of the samples were recorded and compared to each other.…”

Section: Resultsmentioning

confidence: 99%

Complete ablation of tumors using synchronous chemoradiation with bimetallic theranostic nanoparticles

Nosrati

Attari

Abhari

et al. 2022

Bioactive Materials

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Synchronous chemotherapy and radiotherapy, termed chemoradiation therapy, is now an important standard regime for synergistic cancer treatment. For such treatment, nanoparticles can serve as improved carriers of chemotherapeutics into tumors and as better radiosensitizers for localized radiotherapy. Herein, we designed a Schottky-type theranostic heterostructure, Bi 2 S 3 –Au, with deep level defects (DLDs) in Bi 2 S 3 as a nano-radiosensitizer and CT imaging contrast agent which can generate reactive free radicals to initiate DNA damage within tumor cells under X-ray irradiation. Methotrexate (MTX) was conjugated onto the Bi 2 S 3 –Au nanoparticles as a chemotherapeutic agent showing enzymatic stimuli-responsive release behavior. The designed hybrid system also contained curcumin (CUR), which cannot only serve as a nutritional supplement for chemotherapy, but also can play an important role in the radioprotection of normal cells. Impressively, this combined one-dose chemoradiation therapeutic injection of co-drug loaded bimetallic multifunctional theranostic nanoparticles with a one-time clinical X-ray irradiation, completely eradicated tumors in mice after approximately 20 days after irradiation showing extremely effective anticancer efficacy which should be further studied for numerous anti-cancer applications.

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“…In a 2020 study, MTX and MAN were coupled together via an esterification reaction to form MTX-MAN conjugates. Anti-solvent method resulted in the formation of uniform spherical NPs in aqueous solutions with a thin shell composed of large amounts of MAN on the surface [162]. The size and zeta potential of MTX-MAN NPs were around 100 nm and -28 mV, respectively.…”

Section: Conjugation With Carbohydratesmentioning

confidence: 99%

Carrier-free nanodrugs for safe and effective cancer treatment

Karaosmanoglu

Zhou

Shi

et al. 2021

Journal of Controlled Release

118

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Clinical applications of many anti-cancer drugs are restricted due to their hydrophobic nature, requiring use of harmful organic solvents for administration, and poor selectivity and pharmacokinetics resulting in off-target toxicity and inefficient therapies. A wide variety of carrier-based nanoparticles have been developed to tackle these issues, but such strategies often fail to encapsulate drug efficiently and require significant amounts of inorganic and/or organic nanocarriers which may cause toxicity problems in the long term. Preparation of nanoformulations for the delivery of water insoluble drugs without using carriers is thus desired, 2 requiring elegantly designed strategies for products with high quality, stability and performance. These strategies include simple self-assembly or involving chemical modifications via coupling drugs together or conjugating them with various functional molecules such as lipids, carbohydrates and photosensitizers. During nanodrugs synthesis, insertion of redox-responsive linkers and tumor targeting ligands endows them with additional characteristics like on-target delivery, and conjugation with immunotherapeutic reagents enhances immune response alongside therapeutic efficacy. This review aims to summarize the methods of making carrier-free nanodrugs from hydrophobic drug molecules, evaluating their performance, and discussing the advantages, challenges, and future development of these strategies.

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Dual-self-recognizing, stimulus-responsive and carrier-free methotrexate–mannose conjugate nanoparticles with highly synergistic chemotherapeutic effects

Abstract: Stimulus-responsive carrier-free MTX–MAN conjugate nanoparticles could be expected to achieve dual-receptor-mediated self-recognizing, reduced drug dosage, and enhanced synergistic chemotherapeutic effects.

Cited by 31 publications

References 36 publications

Trojan-Horse Diameter-Reducible Nanotheranostics for Macroscopic/Microscopic Imaging-Monitored Chemo-Antiangiogenic Therapy

Trojan-Horse Diameter-Reducible Nanotheranostics for Macroscopic/Microscopic Imaging-Monitored Chemo-Antiangiogenic Therapy

Complete ablation of tumors using synchronous chemoradiation with bimetallic theranostic nanoparticles

Carrier-free nanodrugs for safe and effective cancer treatment

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