Amorphous Oxyhalide Matters for Achieving Lithium Superionic Conduction.

The recently surged halide-based solid electrolytes (SEs) are great candidates for high-performance all-solid-state batteries (ASSBs), due to their decent ionic conductivity, wide electrochemical stability window, and good compatibility with high-voltage oxide cathodes. In contrast to the crystalline phases in halide SEs, amorphous components are rarely understood but play an important role in Li-ion conduction. Here, we reveal that the presence of amorphous component is common in halide-based SEs that are prepared via mechanochemical method. The fast Li-ion migration is found to be associated with the local chemistry of the amorphous proportion. Taking Zr-based halide SEs as an example, the amorphization process can be regulated by incorporating O, resulting in the formation of corner-sharing Zr-O/Cl polyhedrons. This structural configuration has been confirmed through X-ray absorption spectroscopy, pair distribution function analyses, and Reverse Monte Carlo modeling. The unique structure significantly reduces the energy barriers for Li-ion transport. As a result, an enhanced ionic conductivity of (1.35 ± 0.07) × 10-3 S cm-1 at 25 °C can be achieved for amorphous Li3ZrCl4O1.5. In addition to the improved ionic conductivity, amorphization of Zr-based halide SEs via incorporation of O leads to good mechanical deformability and promising electrochemical performance. These findings provide deep insights into the rational design of desirable halide SEs for high-performance ASSBs.

Precise Tailoring of Lithium-Ion Transport for Ultralong-Cycling Dendrite-Free All-Solid-State Lithium Metal Batteries.

All-solid-state lithium metal batteries can address crucial challenges regarding insufficient battery cycling life and energy density. The demonstration of long-cycling dendrite-free all-solid-state lithium metal batteries requires precise tailoring of lithium-ion transport of solid-state electrolytes (SSEs). In this work, a proof of concept is reported for precise tailoring of lithium-ion transport of a halide SSE, Li3InCl6, including intragranular (within grains) but also intergranular (between grains) lithium-ion transport. Lithium-ion migration tailoring mechanism in crystals is developed by unexpected enhanced Li, In, and Cl vacancy populations and lower energy barrier for hopping. The lithium-ion transport tailoring mechanism between the grains is determined by the elimination of voids between grains and the formation of unexpected supersonic conducting grain boundaries, boosting the lithium dendrite suppression ability of SSE. Due to boosted lithium-ion conduction and dendrite-suppression ability, the all-solid-state lithium metal batteries coupled with Ni-rich LiNi0.83Co0.12Mn0.05O2 cathodes and lithium metal anodes demonstrate breakthroughs in electrochemical performance by achieving extremely long cycling life at a high current density of 0.5 C (2000 cycles, 93.7% capacity retention). This concept of precise tailoring of lithium-ion transport provides a cost, time, and energy efficient solution to conquer the remaining challenges in all-solid-state lithium-metal batteries for fast developing electric vehicle markets.

Halide Heterogeneous Structure Boosting Ionic Diffusion and High-Voltage Stability of Sodium Superionic Conductors.

The development of solid-state sodium-ion batteries (SSSBs) heavily hinges on the development of an superionic Na+ conductor (SSC) that features high conductivity, (electro)chemical stability, and deformability. The construction of heterogeneous structures offers a promising approach to comprehensively enhancing these properties in a way that differs from traditional structural optimization. Here, this work exploits the structural variance between high- and low-coordination halide frameworks to develop a new class of halide heterogeneous structure electrolytes (HSEs). The halide HSEs incorporating a UCl3 -type high-coordination framework and amorphous low-coordination phase achieves the highest Na+ conductivity (2.7 mS cm-1 at room temperature, RT) among halide SSCs so far. By discerning the individual contribution of the crystalline bulk, amorphous region, and interface, this work unravels the synergistic ion conduction within halide HSEs and provides a comprehensive explanation of the amorphization effect. More importantly, the excellent deformability, high-voltage stability, and expandability of HSEs enable effective SSSB integration. Using a cold-pressed cathode electrode composite of uncoated Na0.85 Mn0.5 Ni0.4 Fe0.1 O2 and HSEs, the SSSBs present stable cycle performance with a capacity retention of 91.0% after 100 cycles at 0.2 C.

Lithium-compatible and air-stable vacancy-rich Li9N2Cl3 for high-areal capacity, long-cycling all-solid-state lithium metal batteries.

Attaining substantial areal capacity (>3 mAh/cm2) and extended cycle longevity in all-solid-state lithium metal batteries necessitates the implementation of solid-state electrolytes (SSEs) capable of withstanding elevated critical current densities and capacities. In this study, we report a high-performing vacancy-rich Li9N2Cl3 SSE demonstrating excellent lithium compatibility and atmospheric stability and enabling high-areal capacity, long-lasting all-solid-state lithium metal batteries. The Li9N2Cl3 facilitates efficient lithium-ion transport due to its disordered lattice structure and presence of vacancies. Notably, it resists dendrite formation at 10 mA/cm2 and 10 mAh/cm2 due to its intrinsic lithium metal stability. Furthermore, it exhibits robust dry-air stability. Incorporating this SSE in Ni-rich LiNi0.83Co0.11Mn0.06O2 cathode-based all-solid-state batteries, we achieve substantial cycling stability (90.35% capacity retention over 1500 cycles at 0.5 C) and high areal capacity (4.8 mAh/cm2 in pouch cells). These findings pave the way for lithium metal batteries to meet electric vehicle performance demands.

Superionic Conducting Halide Frameworks Enabled by Interface-Bonded Halides.

The revival of ternary halides Li-M-X (M = Y, In, Zr, etc.; X = F, Cl, Br) as solid-state electrolytes (SSEs) shows promise in realizing practical solid-state batteries due to their direct compatibility toward high-voltage cathodes and favorable room-temperature ionic conductivities. Most of the reported superionic halide SSEs have a structural pattern of [MCl6]x- octahedra and generate a tetrahedron-assisted Li+ ion diffusion pathway. Here, we report a new class of zeolite-like halide frameworks, SmCl3, for example, in which 1-dimensional channels are enclosed by [SmCl9]6- tricapped trigonal prisms to provide a short jumping distance of 2.08 Å between two octahedra for Li+ ion hopping. The fast Li+ diffusion along the channels is verified through ab initio molecular dynamics simulations. Similar to zeolites, the SmCl3 framework can be grafted with halide species to obtain mobile ions without altering the base structure, achieving an ionic conductivity over 10-4 S cm-1 at 30 °C with LiCl as the adsorbent. Moreover, the universality of the interface-bonding behavior and ionic diffusion in a class of framework materials is demonstrated. It is suggested that the ionic conductivity of the MCl3/halide composite (M = La-Gd) is likely in correlation with the ionic conductivity of the grafted halide species, interfacial bonding, and framework composition/dimensions. This work reveals a potential class of halide structures for superionic conductors and opens up a new frontier for constructing zeolite-like frameworks in halide-based materials, which will promote the innovation of superionic conductor design and contribute to a broader selection of halide SSEs.

Research on Hybrid Force Control of Redundant Manipulator with Reverse Task Priority.

This paper presents the reverse priority impedance control of manipulators with reference to redundant robots of a given task. The reverse priority kinematic control of redundant manipulators is first expressed in detail. The motion in the joint space is derived following the opposite order compared with the classical task priority-based solution. Then the Cartesian impedance control is combined with the reverse priority impedance control to solve the reverse hierarchical impedance controlled, so that the Cartesian impedance behavior can be divided into the primary priority impedance control and the secondary priority impedance control. Furthermore, the secondary impedance control task will not disturb the primary impedance control task. The motion in the joint space is affected following the opposite order and working in the corresponding projection operators. The primary impedance control tasks are implemented at the end, so as to avoid the possible deformations caused by the singularities occurring in the secondary impedance control tasks. Hence, the proposed reverse priority impedance control of manipulator can achieve the desired impedance control tasks with proper hierarchy. In this paper, the simulation experiments of the manipulator will verify the proposed reverse priority control algorithm.

Realizing High-Performance Li-S Batteries through Additive Manufactured and Chemically Enhanced Cathodes.

Numerous efforts are made to improve the reversible capacity and long-term cycling stability of Li-S cathodes. However, they are susceptible to irreversible capacity loss during cycling owing to shuttling effects and poor Li+ transport under high sulfur loading. Herein, a physically and chemically enhanced lithium sulfur cathode is proposed to address these challenges. Additive manufacturing is used to construct numerous microchannels within high sulfur loading cathodes, which enables desirable deposition mechanisms of lithium polysulfides and improves Li+ and e- transport. Concurrently, cobalt sulfide is incorporated into the cathode composition and demonstrates strong adsorption behavior toward lithium polysulfides during cycling. As a result, excellent electrochemical performance is obtained by the design of a physically and chemically enhanced lithium sulfur cathode. The reported electrode, with a sulfur loading of 8 mg cm-2 , delivers an initial capacity of 1118.8 mA h g-1 and a reversible capacity of 771.7 mA h g-1 after 150 cycles at a current density of 3 mA cm-2 . This work demonstrates that a chemically enhanced sulfur cathode, manufactured through additive manufacturing, is a viable pathway to achieve high-performance Li-S batteries.

New Insights into the High-Performance Black Phosphorus Anode for Lithium-Ion Batteries.

Black phosphorus (BP) is a promising anode material in lithium-ion batteries (LIBs) owing to its high electrical conductivity and capacity. However, the huge volume change of BP during cycling induces rapid capacity fading. In addition, the unclear electrochemical mechanism of BP hinders the development of rational designs and preparation of high-performance BP-based anodes. Here, a high-performance nanostructured BP-graphite-carbon nanotubes composite (BP/G/CNTs) synthesized using ball-milling method is reported. The BP/G/CNTs anode delivers a high initial capacity of 1375 mA h g-1 at 0.15 A g-1 and maintains 1031.7 mA h g-1 after 450 cycles. Excellent high-rate performance is demonstrated with a capacity of 508.1 mA h g-1 after 3000 cycles at 2 A g-1 . Moreover, for the first time, direct evidence is provided experimentally to present the electrochemical mechanism of BP anodes with three-step lithiation and delithiation using ex situ X-ray diffraction (XRD), ex situ X-ray absorption spectroscopy (XAS), ex situ X-ray emission spectroscopy, operando XRD, and operando XAS, which reveal the formation of Li3 P7 , LiP, and Li3 P. Furthermore, the study indicates an open-circuit relaxation effect of the electrode with ex situ and operando XAS analyses.

Platinum complexes of curcumin delivered by dual-responsive polymeric nanoparticles improve chemotherapeutic efficacy based on the enhanced anti-metastasis activity and reduce side effects.

Platinum-based chemotherapy is used for non-small cell lung cancer (NSCLC). However, it has side effects and minimum efficacy against lung cancer metastasis. In this study, platinum-curcumin complexes were loaded into pH and redox dual-responsive nanoparticles (denoted as Pt-CUR@PSPPN) to facilitate intracellular release and synergistic anti-cancer effects. Pt-CUR@PSPPN was prepared by a nano-precipitation method and had a diameter of ∼100 nm. The nanoparticles showed increased anti-cancer effects both in vivo and in vitro. In addition, Pt-CUR@PSPPN blocked PI3K/AKT signal transduction pathway and inhibited MMP2 and VEGFR2, resulting in enhanced anti-metastatic activity. Furthermore, reduced side effects were also observed. In conclusion, Pt-CUR@PSPPN provided a novel and attractive therapeutic strategy for NSCLC.

One-pot synthesis of a microporous organosilica-coated cisplatin nanoplatform for HIF-1-targeted combination cancer therapy.

Nanoparticle formulations have proven effective for cisplatin delivery. However, the development of a versatile nanoplatform for cisplatin-based combination cancer therapies still remains a great challenge. Methods: In this study, we developed a one-pot synthesis method for a microporous organosilica shell-coated cisplatin nanoplatform using a reverse microemulsion method, and explored its application in co-delivering acriflavine (ACF) for inhibiting hypoxia-inducible factor-1 (HIF-1). Results: The resulting nanoparticles were tunable, and they could be optimized to a monodisperse population of particles in the desired size range (40-50 nm). In addition, organic mPEG2000-silane and tetrasulfide bond-bridged organosilica were integrated into the surface and silica matrix of nanoparticles for prolonged blood circulation and tumor-selective glutathione-responsive degradation, respectively. After reaching the tumor sites, cisplatin induced cancer cell death and activated HIF-1 pathways, resulting in acquired drug resistance and tumor metastasis. To address this issue, ACF was co-loaded with cisplatin to prevent the formation of HIF-1α/ß dimers and suppress HIF-1 function. Hence, the efficacy of cisplatin was improved, and cancer metastasis was inhibited. Conclusion: Both in vitro and in vivo results suggested that this core-shell nanostructured cisplatin delivery system represented a highly efficacious and promising nanoplatform for the synergistic delivery of combination therapies involving cisplatin.

Biocompatible co-loading vehicles for delivering both nanoplatin cores and siRNA to treat hepatocellular carcinoma.

Bmi-1 is a gene related to malignant transformation in hepatocellular carcinoma (HCC). The liver cancer cells developed the ability to tolerate CDDP treatment with the elevation of Bmi-1. Bmi-1 is also an oncogene promoting malignance of tumor and an anti-cancer target in many studies. Herein, a biocompatible nanocarrier was designed in the study to deliver a chemotherapeutical agent CDDP and Bmi-1 siRNA to kill cancer cells and silence drug resistance related gene simultaneously. Calciumphosphate (CaP) was applied to coat both nanoplatin cores and siRNA as a shell for the purpose of delivering cargos to the cytosol of the tumor cells. Nanoplatin and siRNA co-loaded CaP nanoparticles (NPSC) enhanced cell uptake of CDDP and showed elevated drug accumulation in tumor. NPSC achieved considerable anti-cancer efficacy and counter-regulated drug tolerance, therefore, warranted a further investigation as a novel therapeutic nanosystem to improve cancer therapy.

Selenium-doped calcium carbonate nanoparticles loaded with cisplatin enhance efficiency and reduce side effects.

Osteosarcoma is the bone tumor that most commonly affects children and teenagers with low survival rate because of metastatic relapse or recurrence. Cisplatin is a first-line chemotherapy for osteosarcoma. However, severe side effects limit its use in clinic. Selenium (Se) is an anticarcinogen that can protect normal tissues from side effects of chemotherapy. In this study, nanoparticles were used to co-deliver cisplatin and Se in a synergistic combination. Se-doped and lipid-coated calcium carbonate nanoparticles loaded with cisplatin (Pt/Se@CaCO3 NPs) were prepared by a reverse microemulsion method. The NPs delivered cisplatin and Se to tumour cells at an optimal synergistic ratio of 1:1 (mol/mol) both in vitro and in an osteosarcoma xenograft model. These results demonstrate that Pt/Se@CaCO3 NPs have great prospects for the osteosarcoma therapy.

Enhancement of cisplatin efficacy by lipid-CaO2 nanocarrier-mediated comprehensive modulation of the tumor microenvironment.

Hypoxia, acidosis and high level of glutathione (GSH) are characteristic abnormalities of the tumor microenvironment (TME), which promote tumor progression, metastasis, and resistance to therapies. Previous attempts to improve therapeutic efficacy were limited to modifying individual TME elements. In this study, we proposed a comprehensive TME modulation strategy that modifies multiple elements of the TME in order to enhance cisplatin anticancer efficacy. To do so, we prepared biocompatible lipid-coated CaO2/cisplatin nanoparticles (LipoCaO2/DDP) by the reverse microemulsion method. We imbued CaO2 with the following reverse-TME properties: O2 generation, increased pH value in tumor cells, and oxidation of intracellular glutathione. In vitro experiments showed that LipoCaO2/DDP could deplete GSH for preventing the binding of GSH to cisplatin. Simultaneously, CaO2 could significantly downregulate multidrug resistance-associated protein 2 (MRP2) by O2-dependent hypoxia-inducible factor 1 (HIF-1) inactivation. Hence, the complete drug-efflux pathway was blocked, and the anticancer effect of cisplatin was enhanced both in vitro and in vivo. Herein, we not only demonstrated the GSH depletion capacity of CaO2 for the first time, but also provided a new comprehensive therapeutic strategy to overcome therapeutic resistance caused by multiple factors in the TME.

Synergism of cisplatin-oleanolic acid co-loaded calcium carbonate nanoparticles on hepatocellular carcinoma cells for enhanced apoptosis and reduced hepatotoxicity.

Background: Cisplatin (CDDP), a widely used chemotherapeutic agent against hepatocellular carcinoma (HCC), faces severe resistance and hepatotoxicity problems which can be alleviated through combination therapy. Purpose: The objective of this study was to develop a pH-dependent calcium carbonate nano-delivery system for the combination therapy of CDDP with oleanolic acid (OA). Methods: A microemulsion method was employed to generate lipid coated cisplatin/oleanolic acid calcium carbonate nanoparticles (CDDP/OA-LCC NPs), and the loading concentration of CDDP and OA was measured by atomic absorption spectroscopy and HPLC respectively.Transmission electron microscopy (TEM) was used to examine the nanoparticles morphology while its pH dependent release characteristics were investigated through in vitro release study. Cellular uptake was examined through a fluorescence microscopy. Apoptotic assays and western blot analysis were conducted to explore the synergistic apoptotic effect of OA on CDDP against HCC cells. The hepatoprotective of OA for CDDP was evaluated through H&E staining. Results: TEM analysis revealed nanoparticles spherical shape with an average particle size of 206±15 nm, and the overall entrapment efficiency was 63.70%±3.9%. In vitro drug release study confirmed the pH-dependent property of the formulation, with the maximum CDDP release of 70%±4.6% at pH 5.5, in contrast to 28%±4.1% CDDP release at pH 7.4. Annexin V-FITC/PI assay and cell cycle analysis confirmed that CDDP and OA synergistically promoted greater HepG2 cells apoptosis for the CDDP/OA-LCC NPs as compared to their individual free drug solutions and NPs-treated groups. Western blot analysis also proved that CDDP/OA-LCC NPs induced the apoptosis by enhancing the proapoptotic protein expressions through downregulating P13K/AKT/mTOR pathway and upregulating p53 proapoptotic pathway. OA helped CDDP to overcome the resistance by downregulating the expression of proteins like XIAP, Bcl-2 via NF-κB pathway. OA also significantly alleviated CDDP-induced hepatotoxicity as evident from the decreased alanine transaminase, aspartate transaminase levels and histochemical evaluation. The possible mechanism may be related to the Nrf-2 induction via its antioxidant mechanism to maintain the redox balance and reduction in CYP2E1 activity which can lead to ROS-mediated oxidative stress. Conclusion: These results suggest that CDDP/OA-LCC NPs have promising applications for co-delivering CDDP and OA to synergize their anti-tumor activity against HCC and to utilize OA's protective effect against CDDP-induced hepatotoxicity.

An Isolated Zinc-Cobalt Atomic Pair for Highly Active and Durable Oxygen Reduction.

A competitive complexation strategy has been developed to construct a novel electrocatalyst with Zn-Co atomic pairs coordinated on N doped carbon support (Zn/CoN-C). Such architecture offers enhanced binding ability of O2 , significantly elongates the O-O length (from 1.23 Što 1.42 Å), and thus facilitates the cleavage of O-O bond, showing a theoretical overpotential of 0.335 V during ORR process. As a result, the Zn/CoN-C catalyst exhibits outstanding ORR performance in both alkaline and acid conditions with a half-wave potential of 0.861 and 0.796 V respectively. The in situ XANES analysis suggests Co as the active center during the ORR. The assembled zinc-air battery with Zn/CoN-C as cathode catalyst presents a maximum power density of 230 mW cm-2 along with excellent operation durability. The excellent catalytic activity in acid is also verified by H2 /O2 fuel cell tests (peak power density of 705 mW cm-2 ).

A high-energy sulfur cathode in carbonate electrolyte by eliminating polysulfides via solid-phase lithium-sulfur transformation.

Carbonate-based electrolytes demonstrate safe and stable electrochemical performance in lithium-sulfur batteries. However, only a few types of sulfur cathodes with low loadings can be employed and the underlying electrochemical mechanism of lithium-sulfur batteries with carbonate-based electrolytes is not well understood. Here, we employ in operando X-ray absorption near edge spectroscopy to shed light on a solid-phase lithium-sulfur reaction mechanism in carbonate electrolyte systems in which sulfur directly transfers to Li2S without the formation of linear polysulfides. Based on this, we demonstrate the cyclability of conventional cyclo-S8 based sulfur cathodes in carbonate-based electrolyte across a wide temperature range, from -20 °C to 55 °C. Remarkably, the developed sulfur cathode architecture has high sulfur content (>65 wt%) with an areal loading of 4.0 mg cm-2. This research demonstrates promising performance of lithium-sulfur pouch cells in a carbonate-based electrolyte, indicating potential application in the future.

Carbon nanofiber interlayer: a highly effective strategy to stabilize silicon anodes for use in lithium-ion batteries.

Silicon (Si) possesses the highest theoretical capacity as an anode material for lithium-ion batteries, and many efforts have been made to address the poor cycling stability issue that is associated with its huge volume changes during Li-Si alloying/de-alloying processes, mostly through the design of nanostructured materials. Herein, we report a simple cell configuration approach to improve the lithium storage performance of commercial nano-Si through the insertion of carbon nanofiber films (CNFs) as interlayers between the Si electrodes and separators. For this advanced cell configuration, commercial Si nanoparticle (Si NP) electrodes demonstrate a significantly improved reversible capacity (2700 mA h g-1 after 40 cycles at 50 mA g-1) and an ultralong cycle life (1250 mA h g-1 after 430 cycles at 1500 mA g-1). Even when cycled at 4 A g-1, the material still demonstrates a very high capacity of 870 mA h g-1. The excellent electrochemical performance of the Si NPs is attributed to the novel cell configuration. Macropores between the carbon nanofibers provide good access of the electrolyte to the Si NP electrodes. The 3D interconnected networks of the CNF interlayer not only decrease the internal charge transfer resistance and enhance the electron transport rate but also offer electron pathways along the CNF interlayer for cracked and disconnected Si NPs after cycling.

Co-delivery of doxorubicin and imatinib by pH sensitive cleavable PEGylated nanoliposomes with folate-mediated targeting to overcome multidrug resistance.

Multidrug resistance to chemotherapeutic drugs is a major obstacle to breast cancer treatment. In this study, doxorubicin (DOX) and imatinib (IM) were co-loaded into folate receptor targeted (FR-targeted) pH-sensitive liposomes (denoted as FPL-DOX/IM) to fulfill intracellular acid-sensitive release and reverse drug resistance. FPL-DOX/IM could maintain stability in blood circulation with approximate diameters of 100 nm and rapidly release encapsulated drugs in tumor acidic microenvironment. Moreover, the IM in combination therapy could overcome chemoresistance associated with DOX effectively by inhibiting ABC transporter function and improving chemotherapy sensitivity. The designed liposomes co-loaded with DOX and IM significantly enhanced anti-tumor effects both in vitro and in vivo. These findings suggest that FPL-DOX/IM provides a novel strategy to improve chemotherapeutic efficacy against MDR tumors.

Enhancing anti-tumor efficiency in hepatocellular carcinoma through the autophagy inhibition by miR-375/sorafenib in lipid-coated calcium carbonate nanoparticles.

Sorafenib is a first-line drug for hepatocellular carcinoma (HCC). Autophagy has been shown to facilitate sorafenib resistance. miR-375 has been shown to be an inhibitor of autophagy. In this study, miR-375 and sorafenib were co-loaded into calcium carbonate nanoparticles with lipid coating (miR-375/Sf-LCC NPs). The nanoparticles had high loading efficiency and were ∼50 nm in diameter. Besides, the NPs could increase the stability and residence time of both drugs. Moreover, we demonstrated that autophagy was activated in HCC cells by sorafenib but not by miR-375/Sf-LCC NPs. In vitro, miR-375/Sf-LCC NPs exhibited pH-dependent drug release and potent cytotoxicity. In vivo, miR-375/Sf-LCC NPs increased miR-375 and sorafenib uptake in tumor (2 folds compared with Lipofectamine 2000-miR-375 and 2-5 folds compared with free sorafenib). Furthermore, miR-375/Sf-LCC NPs showed greatly enhanced therapeutic efficacy in an HCC xenograft model. These findings suggest that miR-375/Sf-LCC NPs may be a promising agent for the HCC therapy. STATEMENT OF SIGNIFICANCE: Hepatocellular carcinoma (HCC) is the most common primary liver tumor and the third leading cause of cancer mortality globally. In this manuscript, miR-375 and sorafenib were co-loaded into calcium carbonate nanoparticles with lipid coating (miR-375/Sf-LCC NPs) to treat HCC. We demonstrated that miR-375/Sf-LCC NPs can deliver sorafenib and miR-375 into HCC cells and tumor tissues, increase drug retention time in tumor, significantly inhibit autophagy and produce enhanced anti-tumor effect.

MiR-375 delivered by lipid-coated doxorubicin-calcium carbonate nanoparticles overcomes chemoresistance in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent and lethal disease that is characterized by drug resistance. Doxorubicin (DOX) is a widely used chemotherapeutic drug and miR-375 has been shown to be a tumor suppressor in HCC. Here, we reported that miR-375 and DOX co-loaded into lipid-coated calcium carbonate nanoparticles (LCC-DOX/miR-375 NPs), enhanced the anti-tumor effects through combination therapy, and were highly effective in reversing drug resistance in HCC. LCC-DOX/miR-375 NPs were prepared by a reverse microemulsions method. In vitro, LCC-DOX/miR-375 NPs exhibited enhanced intracellular accumulation, pH-sensitive DOX release and potent cytotoxicity. In vivo, LCC-DOX/miR-375 NPs showed efficient antitumor effect both in xenograft and primary HCC murine models. Our results showed that the LCC-DOX/miR-375 nanoparticles provide a novel strategy to overcome the drug resistance and promote addictive effect between miR-375 and DOX in HCC.