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

Abstract

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.

Biomimetic dual-responsive bioengineered nanotheranostics for intracellular cascade-synthesizing chemo-drugs and efficient oncotherapy

“…Hence, these experimental results demonstrated that RBCs@ICG-DHN indeed had excellent physiological stability in PBS (pH 7.4), DMEM, and DMEM containing 10% FBS, suggesting that RBCs@ICG-DHN might still retain an intact nanostructure during in vivo blood circulation, and meanwhile could provide a prerequisite for the ERR effect and tumor enrichment. 15 Moreover, these results also confirmed that the hydrogen bond-driven supramolecular recognition between DHN and ICG played a critical role in ICG-DHN formation, while RBCs efficiently enhanced the dispersity, integrity, and physiological stability of the RBCs@ICG-DHN.…”

“…Recently, supramolecular co-assembly nanotechnology has garnered much attention in the development of new theranostic delivery nanoplatforms for precise biomedicine. 23,24 In our study, the vehicle-free ICG-DHN was constructed by a weak interaction-driven supramolecular co-assembly between the nontoxic hydrophobic DHN and FDA-approved amphiphilic photosensitizer ICG (Scheme 1B). To construct ICG-DHN, the nontoxic hydrophobic DHN and amphiphilic photosensitizer ICG were dissolved in a mixed organic solvent, followed by injecting the organic solvent dropwise into an aqueous solution under stirring.…”

“…3 However, these vehicle-free nanotheranostics co-assembled only via weak interactions still suffer from physiological instability and critical premature drug leakage. 14 To address this issue, although our group found and verified that vehicle-free metal–organic nanotheranostics not only showed remarkably enhanced structural integrity and stability but also reduced drug leakage during in vivo blood circulation, 15,16 nevertheless, directly exposing such vehicle-free nanotheranostics in the blood circulation system will inevitably suffer from rapid blood clearance due to immune surveillance, which will significantly reduce the delivery efficiency of vehicle-free nanotheranostics to tumor regions. 17–19 To ameliorate this conflict between vehicle and vehicle-free nanotheranostics, the addition of trace amounts of various natural biological membranes cloaked on the surface of vehicle-free nanotheranostics to obtain bomimetic nanotheranostics has emerged as a promising alternative.…”

Platinum-Coordinated Engineered Nanoreactors with O2 Self-Amplificationand On-Demand Cascade Chemo-Drug Synthesis for Self-Reinforcing Hypoxic Oncotherapy

“…As shown in Figure S5, the D h of IPD was stabilized within water, Dulbecco’s Modified Eagle Medium (DMEM), and DMEM containing 10% fetal bovine serum (FBS) for 24 h. Moreover, it was worth noting that both the D h and PDI of IPD remained virtually unchanged when cultured with water, DMEM, and DMEM + 10% FBS for 5 days (Figure D,E). The results of these experiments combined with previous research showed that IPD could avoid drug leakage in the blood circulation system due to the dynamic coordination interactions. , Considering that poor photostability, rapid degradation, and concentration-dependent aggregation of ICG seriously restrict its further application, , the photostability profile of IPD was also evaluated by determining the fluorescence intensity of ICG at different intervals. As depicted in Figure F,G, the fluorescence intensity of ICG was attenuated to ca.…”

“…Up to now, chemotherapy remains a primary therapeutic method in clinical oncotherapy . Nevertheless, the majority of chemo-drugs still encounter many innate obstacles such as excessive blood and renal clearance, low tumor-targeting ability, low bioavailability, and non-negligible side effects .…”