Han Lin

Metalloporphyrin-Encapsulated Biodegradable Nanosystems for Highly Efficient Magnetic Resonance Imaging-Guided Sonodynamic Cancer Therapy

Traditional photodynamic therapy (PDT) suffers from the critical issues of low tissue-penetrating depth of light and potential phototoxicity, which are expected to be solved by developing new dynamic therapy-based therapeutic modalities such as sonodynamic therapy (SDT). In this work, we report on the design/fabrication of a high-performance multifunctional nanoparticulate sonosensitizer for efficient in vivo magnetic resonance imaging (MRI)-guided SDT against cancer. The developed approach takes the structural and compositional features of mesoporous organosilica-based nanosystems for the fabrication of sonosensitizers with intriguing theranostic performance. The well-defined mesoporosity facilitates the high loading of organic sonosensitizers (protoporphyrin, PpIX) and further chelating of paramagnetic transitional metal Mn ions based on metalloporphyrin chemistry (MnPpIX). The mesoporous structure of large surface area also maximizes the accessibility of water molecules to the encapsulated paramagnetic Mn ions, endowing the composite sonosensitizers with markedly high MRI performance (r1 = 9.43 mM-1 s-2) for SDT guidance and monitoring. Importantly, the developed multifunctional sonosensitizers (HMONs-MnPpIX-PEG) with controllable biodegradation behavior and high biocompatibility show distinctively high SDT efficiency for inducing the cancer-cell death in vitro and suppressing the tumor growth in vivo. This report provides a paradigm that nanotechnology-enhanced SDT based on elaborately designed high-performance multifunctional sonosensitizers will pave a new way for efficient cancer treatment by fully taking the advantages (noninvasiveness, convenience, cost-effectiveness, etc.) of ultrasound therapy and quickly developing nanomedicine.

Two-Dimensional Ultrathin MXene Ceramic Nanosheets for Photothermal Conversion

Ceramic biomaterials have been investigated for several decades, but their potential biomedical applications in cancer therapy have been paid much less attentions, mainly due to their lack of related material functionality for combating the cancer. In this work, we report, for the first time, that MAX ceramic biomaterials exhibit the unique functionality for the photothermal ablation of cancer upon being exfoliated into ultrathin nanosheets within atomic thickness (MXene). As a paradigm, biocompatible Ti3C2 nanosheets (MXenes) were successfully synthesized based on a two-step exfoliation strategy of MAX phase Ti3AlC2 by the combined HF etching and TPAOH intercalation. Especially, the high photothermal-conversion efficiency and in vitro/in vivo photothermal ablation of tumor of Ti3C2 nanosheets (MXenes) were revealed and demonstrated, not only in the intravenous administration of soybean phospholipid modified Ti3C2 nanosheets but also in the localized intratumoral implantation of a phase-changeable PLGA/Ti3C2 organic-inorganic hybrid. This work promises the great potential of Ti3C2 nanosheets (MXenes) as a novel ceramic photothermal agent used for cancer therapy and may arouse much interest in exploring MXene-based ceramic biomaterials to benefit the biomedical applications.

Molecularly organic/inorganic hybrid hollow mesoporous organosilica nanocapsules with tumor-specific biodegradability and enhanced chemotherapeutic functionality

Based on the intrinsic features of high stability and unique multifunctionality, inorganic nanoparticles have shown remarkable potentials in combating cancer, but their biodegradability and biocompatibility are still under debate. As a paradigm, this work successfully demonstrates that framework organic-inorganic hybridization can endow the inorganic mesoporous silica nanocarriers with unique tumor-sensitive biodegradability and high biocompatibility. Based on a chemical homology mechanism, molecularly organic-inorganic hybridized hollow mesoporous organosilica nanocapsules (HMONs) with high dispersity and sub-50xa0nm particle dimension were constructed in mass production. A physiologically active disulfide bond (SS) was directly incorporated into the silica framework, which could break up upon contacting the reducing microenvironment of tumor tissue and biodegrade accordingly. Such a tumor-specific biodegradability is also responsible for the tumor-responsive drug releasing by the fast biodegradation and disintegration of the framework. The ultrasmall particle size of HMONs guarantees their high accumulation into tumor tissue, thus causing the high chemotherapeutic outcome. This research provides a paradigm that framework organic-inorganic hybridization can endow the inorganic nanocarrier with unique biological effects suitable for biomedical application, benefiting the development of novel nanosystems with the unique bio-functionality and performance.

A Two-Dimensional Biodegradable Niobium Carbide (MXene) for Photothermal Tumor Eradication in NIR-I and NIR-II Biowindows

Conventionally, ceramics-based materials, fabricated by high-temperature solid-phase reaction and sintering, are preferred as bone scaffolds in hard-tissue engineering because of their tunable biocompatibility and mechanical properties. However, their possible biomedical applications have rarely been considered, especially the cancer phototherapeutic applications in both the first and second near-infrared light (NIR-I and NIR-II) biowindows. In this work, we explore, for the first time as far as we know, a novel kind of 2D niobium carbide (Nb2C), MXene, with highly efficient in vivo photothermal ablation of mouse tumor xenografts in both NIR-I and NIR-II windows. The 2D Nb2C nanosheets (NSs) were fabricated by a facile and scalable two-step liquid exfoliation method combining stepwise delamination and intercalation procedures. The ultrathin, lateral-nanosized Nb2C NSs exhibited extraordinarily high photothermal conversion efficiency (36.4% at NIR-I and 45.65% at NIR-II), as well as high photothermal stability. The Nb2C NSs intrinsically feature unique enzyme-responsive biodegradability to human myeloperoxidase, low phototoxicity, and high biocompatibility. Especially, these surface-engineered Nb2C NSs present highly efficient in vivo photothermal ablation and eradication of tumor in both NIR-I and NIR-II biowindows. This work significantly broadens the application prospects of 2D MXenes by rationally designing their compositions and exploring related physiochemical properties, especially on phototherapy of cancer.

Theranostic 2D Tantalum Carbide (MXene)

The large-dimensional and rigid ceramic bulks fabricated by high-temperature solid-phase reaction and sintering have never been considered for possibly entering and circulating within the blood vessels for biomedical applications, especially on combating cancer. Here, it is reported for the first time that MAX ceramic biomaterials exhibit unique functionalities for dual-mode photoacoustic/computed tomography imaging and are highly effective for in vivo photothermal ablation of tumors upon being exfoliated into ultrathin nanosheets within atomic thickness (MXene). As a paradigm, 2D ultrathin tantalum carbide nanosheets (Ta4 C3 MXenes) with nanosized lateral sizes are successfully synthesized based on a two-step liquid exfoliation strategy of MAX phase Ta4 AlC3 by combined hydrofluoric acid (HF) etching and probe sonication. The structural, electronic, and surface characteristics of the as-exfoliated nanosheets are revealed by various characterizations combined with first-principles calculations via density functional theory. Especially, the superior photothermal-conversion performance (efficiency η of 44.7%) and in vitro/in vivo photothermal ablation of tumor by biocompatible soybean phospholipid-modified Ta4 C3 nanosheets are systematically revealed and demonstrated. Based on the large family members of MXenes, this work may offer a paradigm that MXenes can achieve the specific biomedical applications (here, theranostic) providing that their compositions and nanostructures are carefully tuned and optimized to meet the strict requirements of biomedicine.

Two-Dimensional Tantalum Carbide (MXenes) Composite Nanosheets for Multiple Imaging-Guided Photothermal Tumor Ablation

MXenes, an emerging family of graphene-analogues two-dimensional (2D) materials, have attracted continuous and tremendous attention in many application fields because of their intrinsic physiochemical properties and high performance in versatile applications. In this work, we report on the construction of tantalum carbide (Ta4C3) MXene-based composite nanosheets for multiple imaging-guided photothermal tumor ablation, which has been achieved by rational choice of the composition of MXenes and their surface functionalization. A redox reaction was activated on the surface of tantalum carbide (Ta4C3) MXene for in situ growth of manganese oxide nanoparticles (MnOx/Ta4C3) based on the reducing surface of the nanosheets. The tantalum components of MnOx/Ta4C3 acted as the high-performance contrast agents for contrast-enhanced computed tomography, and the integrated MnOx component functionalized as the tumor microenvironment-responsive contrast agents for T1-weighted magnetic resonance imaging. The photothermal-conversion performance of MnOx/Ta4C3 composite nanosheets not only has achieved contrast-enhanced photoacoustic imaging, but also realized the significant tumor-growth suppression by photothermal hyperthermia. This work broadens the biomedical applications of MXenes, not only by the fabrication of family members of biocompatible MXenes, but also by the development of functionalization strategies of MXenes for cancer-theranostic applications.

Theranostic 2D ultrathin MnO 2 nanosheets with fast responsibility to endogenous tumor microenvironment and exogenous NIR irradiation

The fabrication of functional nanoparticles with unique ultra-sensitivity to endogenous tumor microenvironment (TME) is of great significance for their improved theranostic performance and easy excretion out of the body, which has not been realized among diverse nano-sized photothermal agents for photothermal therapy (PTT) of tumor. In this work, we report on the synthesis of 2D ultrathin MnO2 nanosheets for highly efficient PTT against tumor with ultra-sensitivity to endogenous TME. These ultrathin 2D MnO2 nanosheets show the intriguing characteristic of disintegration and releasing of Mn2+ in response to the mild acidic condition and elevated reducing microenvironment of TME, which has successfully realized the pH- and reducing-responsive T1-weighted magnetic resonance imaging of tumor. Importantly, the high PTT efficiency of 2D MnO2 nanosheets responsive to exogenous NIR irradiation has been systematically demonstrated both inxa0vitro and inxa0vivo for suppressing the tumor growth. This first report on the exploring of TME-sensitive photothermal agents with concurrent diagnostic and therapeutic (theranostic) functions significantly broadens the biomedical application of 2D functional biomaterials, which also promotes the further potential clinical translations of nano-sized photothermal agents.

2D Ultrathin MXene‐Based Drug‐Delivery Nanoplatform for Synergistic Photothermal Ablation and Chemotherapy of Cancer

Two-dimensional (2D) MXenes, as a new 2D functional material nanosystem, have been extensively explored for broad applications. However, their specific performance and applications in theranostic nanomedicine have still rarely been explored. This work reports on the drug-delivery performance and synergistic therapeutic efficiency of Ti3 C2 MXenes for highly efficient tumor eradication. These Ti3 C2 MXenes not only possess high drug-loading capability of as high as 211.8%, but also exhibit both pH-responsive and near infrared laser-triggered on-demand drug release. Especially, based on the high photothermal-conversion capability of Ti3 C2 MXenes, they have been further explored for efficient tumor eradication by synergistic photothermal ablation and chemotherapy, which has been systematically demonstrated both in vitro and in vivo. These Ti3 C2 MXenes have also been demonstrated as the desirable contrast agents for photoacoustic imaging, showing the potential for diagnostic-imaging guidance and monitoring during therapy. The high in vivo histocompatibility of Ti3 C2 and their easy excretion out of the body have been evaluated and demonstrated, showing the potential high biosafety for further clinical translation. This work paves a new way for broadening biomedical applications of MXenes in nanomedicine where they can exert the high performance and functionality for synergistic therapy, especially on combating cancer.

2D superparamagnetic tantalum carbide composite MXenes for efficient breast-cancer theranostics

Background: The emergence of two-dimensional MXenes has spurred their versatile applications in broad fields, but the exploring of novel MXene-based family members and their potential applications in theranostic nanomedicine (concurrent diagnostic imaging and therapy) have been rarely explored. In this work, we report the construction of a novel superparamagnetic MXene-based theranostic nanoplatform for efficient breast-cancer theranostics, which was based on intriguing tantalum carbide (Ta4C3) MXene and its further rational surface-superparamagnetic iron-oxide functionalization (Ta4C3-IONP-SPs composite MXenes) for efficient breast-cancer theranostic. Methods: The fabrication of ultrathin Ta4C3 nanosheets was based on an exfoliation strategy and superparamagnetic iron oxide nanoparticles were in-situ grown onto the surface of Ta4C3 MXene according to the redox reaction of MXene. Ta4C3-IONP MXenes were modified with soybean phospholipid (SP) to guarantee high stability in physiological conditions. The photothermal therapy, contrast-enhanced CT, T2-weighted magnetic resonance imaging and the high biocompatibility of these composite nanosheets have also been evaluated in vitro at cellular level and in vivo on mice breast tumor allograft tumor model. Results: The Ta component of Ta4C3-IONP-SPs exhibits high performance for contrast-enhanced CT imaging because of its high atomic number and high X-ray attenuation coefficient, and the integrated superparamagnetic IONPs act as excellent contrast agents for T2-weighted magnetic resonance imaging. Especially, these Ta4C3-IONP-SPs composite nanosheets with high photothermal-conversion efficiency (η: 32.5%) has achieved complete tumor eradication without reoccurrence, verifying their highly efficient breast-tumor photo-ablation performance. Conclusion: This work not only significantly broadens the biomedical applications of MXene-based nanoplatforms (Ta4C3 MXene) by exploring their novel family members and further functionalization strategies (magnetic functionalization in this work), but also provides a novel and efficient theranostic nanoplatform for efficient breast-cancer theranostics.

Surface Nanopore Engineering of 2D MXenes for Targeted and Synergistic Multitherapies of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common and deadly gastrointestinal malignancies. Given its insensitivity to traditional systematic chemotherapy, new therapeutic strategies for efficient HCCs treatment are urgently needed. Here, the development of a novel 2D MXene-based composite nanoplatform for highly efficient and synergistic chemotherapy and photothermal hyperthermia against HCC is reported. A surface-nanopore engineering strategy is developed for the MXenes surface functionalization, which achieves the uniform coating of a thin mesoporous-silica layer onto the surface of 2D Ti3 C2 MXene (Ti3 C2 @mMSNs). This strategy endows MXenes with well-defined mesopores for on-demand drug release/delivery, enhanced hydrophilicity/dispersity, and abundant surface chemistry for targeting engineering. Systematic in vitro and in vivo evaluations have demonstrated the high active-targeting capability of arginine-glycine-aspartic acid (RGD)-targeting Ti3 C2 @mMSNs into tumor, and the synergistic chemotherapy (contributed by the mesoporous shell) and photothermal hyperthermia (contributed by the Ti3 C2 MXene core) completely eradicate the tumor without obvious reoccurrence. This work not only provides a novel strategy for efficiently combating HCC by developing MXene-based composite nanoplatforms, but also paves a new way for extending the biomedical applications of MXenes by surface-nanopore engineering.