Tumor Targeting Ability Research Articles

Hybrid FeWO4-Hyaluronic Acid Nanoparticles as a Targeted Nanotheranostic Agent for Multimodal Imaging-Guided Tumor Photothermal Therapy.

Development of versatile nanoplatform still remains a great challenge due to multistep synthesis and complicated compositions. Therefore, it is significant to develop a facile method to synthesize a nanocomposite to achieve multimodal imaging and even imaging-guided cancer therapeutics. In our study, hyaluronic acid-functionalized iron (II) tungstate nanoparticles (HA-FeWO4 NPs) were successfully synthesized as a versatile nanoplatform by a facile one-pot hydrothermal procedure. The formed multifunctional HA-FeWO4 NPs were investigated via a series of characterization techniques, which demonstrated good biocompatibility, excellent dispersion, low cytotoxicity, active tumor-targeting ability and high photothermal efficiency. Furthermore, tumor was clearly visualized by HA-FeWO4 NPs with multimodal imaging of infrared thermal imaging, magnetic resonance imaging, computed tomography imaging in 4T1 tumor bearing mice. More importantly, HA-FeWO4 could achieve multimodal imaging-guided photothermal therapy of 4T1 tumors. The constructed HA-FeWO4 NPs have great potential as ideal nanotheranostic agents for multimodal imaging and even imaging-guided cancer theranostics in biological systems.

Biomimetic platelet nanoparticles encapsulated with proteasome inhibitor bortezomib for multiple myeloma treatment

The discovery of bortezomib (BTZ) has been a major clinical breakthrough for multiple myeloma (MM) treatment. However, its clinical application is restricted to a low tumor-targeting ability, fast clearance, and treatment-related toxicity. Here, we report a targeting strategy of MM by poly(lactic-co-glycolic acid)(PLGA) nanoparticles cloaking with platelet membranes (PMs) encapsulating BTZ (PM/BTZNPs). The drug delivery system could encapsulate sufficient BTZ with suitable nanoparticle characteristics for cellular uptake via an easy fabrication process. Of note, PM coating markedly enhances the selectivity, cellular uptake, and anticancer effects of BTZ in LP-1 cells. PM/BTZNPs further display a targeted drug delivery system to MM, causing a low toxicity effect and exhibiting an obvious survival advantage compared to nontargeted BTZ. Therefore, PM/BTZNPs, as a biomimetic nanotherapeutic formulation, demonstrate a high potential for MM patients.

Design, synthesis, cell imaging, and bioactivity assessment of novel Rhodamine-Pyrimidine nido-carborane derivatives as fluorescent anticancer agents

Because of the advantages of fluorescent drugs consisting of fluorescent dyes and compounds with anticancer activity for therapeutic diagnostics and personalized medicine. A series of fluorescent antitumor drugs rhodamine pyrimidine derivatives (RP1, RP2, RP3 and RP4) were synthesized by linking rhodamine B and pyrimidine derivatives through ethylenediamine bridge and then introduced into nido-carborane to form fluorescent salt derivatives (RPB1, RPB2, RPB3, and RPB4). It improves the tumor targeting and imaging ability of pyrimidine derivatives. By CCK8, it was found that the inhibition rates of RP4 and RPB4 at 10 μg/mL on HeLa, PC-3 and L02 cells were 70.4 %, 68.7 %, 86.1 % and 72.5 %, 76.4 %, 81.0 %, respectively. The compound has strong inhibitory effect on cancer cells. The logP values of compounds RP4 and RPB4 were between 0 and 3, which were easily absorbed and transported through the cell membrane. Further cell imaging experiments showed that RP4 could enter tumor cells through cell membrane and had good biocompatibility. The experimental results show that compounds RP4 has good imaging capability and tumor targeting, and is a potential fluorescent anticancer agents.

Multifunctional hybrid oncolytic virus-mimicking nanoparticles for targeted induce of tumor-specific pyroptosis and enhanced anti-tumor immune response in melanoma

Pyroptosis, a newly discovered form of programmed cell death, has emerged as a promising antitumor approach by releasing pro-inflammatory cytokines and immunogenic substances upon cell rupture. However, non-specific pyroptosis potentially causes systemic damage to healthy tissues, and the heterogeneity of tumors limits the anti-tumor effect of pyroptosis. To address these challenges, we propose a simple yet powerful method for creating multifunctional hybrid oncolytic virus-mimicking nanovesicles (HVMNVs) that possess tumor-targeting capabilities, adjuvant activity, and the ability to evade immune clearance induced by virus modification. Based on this multifunctional nanovesicle, we developed a functional nanoparticle (HVMNVs@Fe-C) that significantly enhances the tumor targetability and cell uptake efficiency of the extremely small iron oxide nanoparticles (ESIONPs) and carbonyl cyanide m-chlorophenyl hydrazone (CCCP), leading to rapid tumor pyroptosis. More importantly, HVMNVs@Fe-C ingeniously achieves a synergistic effect by incorporating the adjuvantic and tumor-targeting properties of oncolytic viruses with the cell lytic and pro-inflammatory functions of pyroptosis in a single nanoparticle. This leads to a cascade of specific anti-tumor immune responses and reprogramming of the immunosuppressive tumor microenvironment, resulting in excellent tumor inhibition efficacy against primary melanoma growth and pulmonary metastasis. Overall, our novel strategy offers considerable promise for precisive targeted delivery and cancer immunotherapy.

Tumor-Targeted Fluorescent/Photoacoustic Imaging of Legumain Activity In Vivo.

Legumain has been identified as a target for diagnosis and treatment of associated cancers. Therefore, real-time imaging of legumain activity in vivo is helpful in diagnosing and evaluating therapeutic efficacy of associated cancers. Fluorescent/photoacoustic (FL/PA) dual-modal imaging developed rapidly because of its good sensitivity and spatial resolution. As far as we know, a tumor-targeted probe for FL/PA imaging of legumain activity in vivo has not been reported. Hence, we intended to develop a tumor-targeted hemicyanine (HCy) probe (HCy-AAN-Bio) for FL/PA imaging of legumain in vivo. The control probe HCy-AAN does not have tumor-targeting ability. Legumain can specifically cleave HCy-AAN-Bio or HCy-AAN with the generation of FL/PA signal while more HCy-AAN-Bio could be recognized by legumain than HCy-AAN with higher sensitivity in vitro. Due to the tumor-targeting ability, HCy-AAN-Bio could image 4T1 cells with an additional 1.3-fold FL enhancement and 1.9-fold PA enhancement than HCy-AAN. In addition, HCy-AAN-Bio could image legumain activity in vivo with an additional 1.5-fold FL enhancement and 1.9-fold PA enhancement than HCy-AAN. We expected that HCy-AAN-Bio will be a powerful tool for early diagnosis of associated cancer.

Manganese Dioxide/Gold-based Active Tumor Targeting Nanoprobes for Enhancing Photodynamic and Low-Temperature-Photothermal Combination Therapy in Lung Cancer.

Tumor drug resistance caused by the tumor microenvironment is an extremely difficult problem for researchers to solve. Nanoplatforms that integrate diagnosis and treatment have great advantages in tumor treatment, but the design and synthesis of simple and efficient nanoplatforms still face tremendous challenges. In this study, a novel Mn/Au@ir820/GA-CD133 nanoprobe was developed. The manganese dioxide/gold particles were prepared by coprecipitation/assembly, chemically coupled with CD133 antibody, and finally loaded with the photosensitive drug IR820 and the heat shock protein inhibitor Ganetespib. The nanoprobe demonstrated good tumor-targeting ability, increased the level of singlet oxygen produced from laser irradiation by effectively alleviating tumor hypoxia, and decreased the threshold of heat tolerance by downregulating the expression of HSP90 in tumor tissues. This nanoprobe successfully inhibited the growth and progression of tumor tissues in a tumor-bearing mouse model by improving the effectiveness of photodynamic and low-temperature photothermal combination therapy.

Core-Shell Reactor Partitioning Enzyme and Prodrug by ZIF-8 for NADPH-Sensitive In Situ Prodrug Activation.

Enzyme-prodrug therapies have shown unique advantages in efficiency, selectivity, and specificity of in vivo prodrug activation. However, precise spatiotemporal control of both the enzyme and its substrate at the target site, preservation of enzyme activity, and in situ substrate depletion due to low prodrug delivery efficiency continue to be great challenges. Here, we propose a novel core-shell reactor partitioning enzyme and prodrug by ZIF-8, which integrates an enzyme with its substrate and increases the drug loading capacity (DLC) using a prodrug as the building ligand to form a Zn-prodrug shell. Cytochrome P450 (CYP450) is immobilized in ZIF-8, and the antitumor drug dacarbazine (DTIC) is coordinated and deposited in its outer layer with a high DLC of 43.6±0.8 %. With this configuration, a much higher prodrug conversion efficiency of CYP450 (36.5±1.5 %) and lower IC50 value (26.3±2.6 μg/mL) are measured for B16-F10 cells with a higher NADPH concentration than those of L02 cells and HUVECs. With the tumor targeting ability of hyaluronic acid, this core-shell enzyme reactor shows a high tumor suppression rate of 96.6±1.9 % and provides a simple and versatile strategy for enabling in vivo biocatalysis to be more efficient, selective, and safer.

Core‐Shell Reactor Partitioning Enzyme and Prodrug by ZIF‐8 for NADPH‐Sensitive In Situ Prodrug Activation

AbstractEnzyme‐prodrug therapies have shown unique advantages in efficiency, selectivity, and specificity of in vivo prodrug activation. However, precise spatiotemporal control of both the enzyme and its substrate at the target site, preservation of enzyme activity, and in situ substrate depletion due to low prodrug delivery efficiency continue to be great challenges. Here, we propose a novel core–shell reactor partitioning enzyme and prodrug by ZIF‐8, which integrates an enzyme with its substrate and increases the drug loading capacity (DLC) using a prodrug as the building ligand to form a Zn‐prodrug shell. Cytochrome P450 (CYP450) is immobilized in ZIF‐8, and the antitumor drug dacarbazine (DTIC) is coordinated and deposited in its outer layer with a high DLC of 43.6±0.8 %. With this configuration, a much higher prodrug conversion efficiency of CYP450 (36.5±1.5 %) and lower IC50 value (26.3±2.6 μg/mL) are measured for B16‐F10 cells with a higher NADPH concentration than those of L02 cells and HUVECs. With the tumor targeting ability of hyaluronic acid, this core–shell enzyme reactor shows a high tumor suppression rate of 96.6±1.9 % and provides a simple and versatile strategy for enabling in vivo biocatalysis to be more efficient, selective, and safer.

DNA aptamer functionalized monodisperse Eu/Mn-WH nanoparticle for in vivo magnetic resonance and fluorescence imaging

Because of its biocompatibility, non-immunogenicity, bioactivity, and biodegradability, Whitlockite (WH) plays a crucial role in biomedical fields. However, a layer of oleic acid molecules is attached to the surface of WH synthesized by liquid–solid–solution (LSS) method, which hinders its application in biomedicine field. In this paper, we successfully synthesized hydrophilic nanoparticles with bright red fluorescence and excellent magnetic properties (Eu/Mn-WH-Apt NPs) via the ions doping and ligand exchange strategy. In vitro/vivo experiments show that Eu/Mn-WH-Apt nanoparticles have excellent biocompatibility, dispersion stability, tumor targeting ability, satisfactory fluorescence, and magnetic resonance imaging capabilities. Therefore, the prepared multifunctional Eu/Mn-WH-Apt NPs may provide a new strategy and insights for accurately diagnosing clinical cancer.

Assessing the effectiveness of fluorinated and α-methylated 3-boronophenylalanine for improved tumor-specific boron delivery in boron neutron capture therapy

A [10B]boron agent and a nuclear imaging probe for pharmacokinetic estimation form the fundamental pair in successful boron neutron capture therapy (BNCT). However, 4-[10B]borono-l-phenylalanine (BPA), used in clinical BNCT, has undesirable water solubility and tumor selectivity. Therefore, we synthesized fluorinated and α-methylated 3-borono-l-phenylalanine (3BPA) derivatives to realize improved water solubility, tumor targetability, and biodistribution. All 3BPA derivatives exhibited over 10 times higher water solubility than BPA. Treatment with α-methylated 3BPA derivatives resulted in decreased cell uptake via l-type amino acid transporter (LAT) 2 while maintaining LAT1 recognition, thereby significantly improving LAT1/LAT2 selectivity. Biodistribution studies showed that fluorinated α-methyl 3BPA derivatives exhibited reduced boron accumulation in nontarget tissues, including muscle, skin, and plasma. Consequently, these derivatives demonstrated significantly improved tumor-to-normal tissue ratios compared to 3BPA and BPA. Overall, fluorinated α-methyl 3BPA derivatives with the corresponding radiofluorinated compounds hold potential as promising agents for future BNCT/PET theranostics.

Results from a Phase 1 Study of ACTR707 in Combination with Rituximab in Patients with Relapsed or Refractory CD20+ B Cell Lymphoma

The antibody-coupled T cell receptor (ACTR) platform is an autologous engineered T cell therapy combining the cell-killing ability of T cells and the tumor-targeting ability of coadministered antibodies. Activation of the T cell product ACTR707 is dependent on the engagement of antibody bound to target cells via the CD16 domain of the chimeric receptor (CD16V-CD28-CD3ζ). ACTR707 in combination with the anti-CD20 monoclonal antibody rituximab was evaluated in the ATTCK-20-03 study, a multisite, single-arm, open-label phase I trial in B cell non-Hodgkin lymphoma (NHL). The primary objectives of this study were to evaluate the safety of the combination of ACTR707 and rituximab and to determine a recommended phase 2 dose (RP2D). Secondary objectives included evaluation of antitumor activity and ACTR T cell persistence. The study design included an ACTR707 cell dose escalation phase and an expansion phase at the RP2D. Escalating dose levels of ACTR707 in combination with rituximab were explored in 5 dose cohorts, with 25 subjects receiving study treatment. Subjects received lymphodepleting chemotherapy (cyclophosphamide 400 mg/m2/day and fludarabine 30 mg/m2/day) for 3 days, followed by rituximab 375 mg/m2 and, 24 to 48 hours later, a single dose of ACTR707. Additional doses of rituximab were administered every 3 weeks until disease progression, unacceptable toxicity, or investigator decision. Blood samples were collected at various time points to assess levels of rituximab, cytokines, inflammatory markers, and ACTR707 T cells. The overall response rate of ACTR707 plus rituximab was 56% (14 of 25) across all dose levels. Ten subjects (40.0%) achieved a complete response, with the longest duration of 586 days (range, 85 to 586 days), and 4 subjects (16.0%) experienced a partial response, with the longest duration of 130 days (range, 44 to 130 days). Only 1 case of cytokine release syndrome (grade 2) and no events of neurotoxicity were reported. There were no dose-limiting toxicities or events leading to death. ACTR707 plus rituximab resulted in only 1 adverse event (neutropenia), leading to study discontinuation of rituximab. The ATTCK-20-03 trial serves as proof of principle regarding the ACTR approach that potentially could be used with other antibodies targeting other markers in other malignancies. Although the ACTR707 program has been discontinued, these results may support other programs in the use of similar novel approaches of antibody-coupled T cell activation.

HIMB1636-MMAE, a Novel TROP2-Targeting Antibody-Drug Conjugate Exerting Potent Antitumor Efficacy in Pancreatic Cancer.

Herein, we first prepared a novel anti-TROP2 antibody-drug conjugate (ADC) hIMB1636-MMAE using hIMB1636 antibody chemically coupled to monomethyl auristatin E (MMAE) via a Valine-Citrulline linker and then reported its characteristics and antitumor activity. With a DAR of 3.92, it binds specifically to both recombinant antigen (KD ∼ 0.687 nM) and cancer cells and could be internalized by target cells and selectively kill them with IC50 values at nanomolar/subnanomolar levels by inducing apoptosis and G2/M phase arrest. hIMB1636-MMAE also inhibited cell migration, induced ADCC effects, and had bystander effects. It displayed significant tumor-targeting ability and excellent tumor-suppressive effects in vivo, resulting in 5/8 tumor elimination at 12 mg/kg in the T3M4 xenograft model or complete tumor disappearance at 10 mg/kg in BxPc-3 xenografts in nude mice. Its half-life in mice was about 87 h. These data suggested that hIMB1636-MMAE was a promising candidate for the treatment of pancreatic cancer with TROP2 overexpression.

Biomimetic Prussian blue nanocomplexes for chemo-photothermal treatment of triple-negative breast cancer by enhancing ICD

Drug-induced immunogenic cell death (ICD) can efficiently inhibit tumor growth and recurrence through the release of tumor-associated antigens which activate both local and systemic immune responses. Pyroptosis has emerged as an effective means for inducing ICD; however, the development of novel pyroptosis inducers to specifically target tumor cells remains a pressing requirement. Herein, we report that Cinobufagin (CS-1), a main ingredient of Chansu, can effectively induce pyroptosis of triple-negative breast cancer (TNBC) cells, making it a potential therapeutic agent for this kind of tumor. However, the application of CS-1 in vivo is extremely limited by the high dosage/long-term usage and non-selectivity caused by systemic toxicity. To address these drawbacks, we developed a new nanomedicine by loading CS-1 into Prussian blue nanoparticles (PB NPs). The nanomedicine can release CS-1 in a photothermal-controlled manner inherited in PB NPs. Furthermore, hybrid membrane (HM) camouflage was adopted to improve the immune escape and tumor-targeting ability of this nanomedicine, as well. In vitro assays demonstrated that the chemo-photothermal combination treatment produced high-level ICD, ultimately fostering the maturation of dendritic cells (DCs). In vivo anti-tumor assessments further indicated that this strategy not only efficiently inhibited primary growth of MDA-MB-231 cells and 4T1 cells-bearing models but also efficiently attenuated distant tumor growth in 4T1 xenograft model. This was mechanistically achieved throuh the promotion of DCs maturation, infiltration of cytotoxic T lymphocyte into the tumor, and the inhibition of Treg cells. In summary, this work provides a novel strategy for efficient TNBC therapy by using nanomaterials-based multimodal nanomedicine through rational design.

Transferrin-Modified Triptolide Liposome Targeting Enhances Anti-Hepatocellular Carcinoma Effects.

Triptolide (TP) is an epoxy diterpene lactone compound isolated and purified from the traditional Chinese medicinal plant Tripterygium wilfordii Hook. f., which has been shown to inhibit the proliferation of hepatocellular carcinoma. However, due to problems with solubility, bioavailability, and adverse effects, the use and effectiveness of the drug are limited. In this study, a transferrin-modified TP liposome (TF-TP@LIP) was constructed for the delivery of TP. The thin-film hydration method was used to prepare TF-TP@LIP. The physicochemical properties, drug loading, particle size, polydispersity coefficient, and zeta potential of the liposomes were examined. The inhibitory effects of TF-TP@LIP on tumor cells in vitro were assessed using the HepG2 cell line. The biodistribution of TF-TP@LIP and its anti-tumor effects were investigated in tumor-bearing nude mice. The results showed that TF-TP@LIP was spherical, had a particle size of 130.33 ± 1.89 nm and zeta potential of -23.20 ± 0.90 mV, and was electronegative. Encapsulation and drug loading were 85.33 ± 0.41% and 9.96 ± 0.21%, respectively. The preparation was stable in serum over 24 h and showed biocompatibility and slow release of the drug. Flow cytometry and fluorescence microscopy showed that uptake of TF-TP@LIP was significantly higher than that of TP@LIP (p < 0.05), while MTT assays indicated mean median inhibition concentrations (IC50) of TP, TP@LIP, and TF-TP@ of 90.6 nM, 56.1 nM, and 42.3 nM, respectively, in HepG2 cell treated for 48 h. Real-time fluorescence imaging indicated a significant accumulation of DiR-labeled TF-TP@LIPs at tumor sites in nude mice, in contrast to DiR-only or DiR-labeled, indicating that modification with transferrin enhanced drug targeting to the tumor tissues. Compared with the TP and TP@LIP groups, the TF-TP@LIP group had a significant inhibitory effect on tumor growth. H&E staining results showed that TF-TP@LIP inhibited tumor growth and did not induce any significant pathological changes in the heart, liver, spleen, and kidneys of nude mice, with all liver and kidney indices within the normal range, with no significant differences compared with the control group, indicating the safety of the preparation. The findings indicated that modification by transferrin significantly enhanced the tumor-targeting ability of the liposomes and improved their anti-tumor effects in vivo. Reducing its distribution in normal tissues and decreasing its toxic effects suggest that the potential of TF-TP@LIP warrants further investigation for its clinical application.

Porphyrin-Based Brain Tumor-Targeting Agents: [64Cu]Cu-porphyrin and [64Cu]Cu-TDAP.

The aim of this study is to evaluate a radioactive metal complex platform for brain tumor targeting. Herein, we introduce a new porphyrin derivative, 5,10,15,20-(tetra-N,N-dimethyl-4-aminophenyl)porphyrin (TDAP), in which four N,N-dimethyl-4-p-phenylenediamine (DMPD) moieties are conjugated to the porphyrin labeled with the radiometal 64Cu. DMPD affected the pharmacokinetics of porphyrin in terms of retention time in vivo and tumor-targeting ability relative to those of unmodified porphyrin. [64Cu]Cu-TDAP showed stronger enhancement than [64Cu]Cu-porphyrin in U87MG glioblastoma cells, especially in the cytoplasm and nucleus, indicating its tumor-targeting properties and potential use as a therapeutic agent. In the subcutaneous and orthotopic models of brain-tumor-bearing mice, [64Cu]Cu-TDAP was clearly visualized in the tumor site via positron emission tomography imaging and showed a tumor-to-brain ratio as high as 13. [64Cu]Cu-TDAP deserves attention as a new diagnostic agent that is suitable for the early diagnosis and treatment of brain tumors.

Tumor-targeted delivery of lnc antisense RNA against RCAS1 by live-attenuated tryptophan-auxotrophic Salmonella inhibited 4T1 breast tumors and metastasis in mice

Emerging chemo- and radiotherapy resistance exacerbated thecancer risk and necessitated novel treatment strategies. Although RNA therapeutics against pro-oncogenic genes are highly effective, tumor-specific delivery remains a barrier to the implementation of this valuable tool. In this study, we report a tryptophan-auxotrophic Salmonella typhimurium strain as an onco-therapeutic delivery system with tumor-targeting ability using 4T1 mice breast-cancer model. The receptor-binding cancer antigen expressed on SiSo cell (RCAS1) is a cancer-specific protein that induces the apoptosis of peripheral lymphocytes and confers tumor immune evasion. We designed a long non-coding antisense-RNA against RCAS1 (asRCAS1) and delivered by Salmonella using a non-antibiotic, auxotrophic-selective, eukaryotic expression plasmid, pJHL204. After invivo tumor-to-tumor passaging, the JOL2888 (ΔtrpA, ΔtrpE, Δasd+ asRCAS1) strain exhibited high sustainability in tumors, but did not last in healthy organs, thereby demonstrating tumor specificity and safety. RCAS1 inhibition in the tumor was confirmed by western blotting and qPCR. In mice, JOL2888 treatment reduced tumor-associated macrophages, improved the Tcell population, elicited cell-mediated immunity, and suppressed cancer-promoting genes. Consequently, the JOL2888 treatment significantly decreased the tumor volume by 80%, decreased splenomegaly by 30%, and completely arrested lung metastasis. These findings highlight the intrinsic tumor-targeting ability of tryptophan-auxotrophic Salmonella for delivering onco-therapeutic macromolecules.

An intercalated covalent organic framework with donor-acceptor property for photothermal therapy

Based on the supramolecular assembly strategy, a donor-acceptor (D-A) covalent organic framework (COF) was developed by intercalating the electron-rich tetrathiafulvalene (TTF) between the layers of the COF which used 1,3,5-tris-(4-aminophenyl)triazine (TAPT) as an electron-deficient building unit. Due to the supramolecular D-A interactions, the obtained intercalated COF can efficiently convert luminous energy into thermal energy with a satisfying photothermal conversion efficiency up to 38.1 % for photothermal therapy. To further improve the biocompatibility and tumor targeting ability, the TTF-intercalated COF was coated with cancer cell membranes. In vitro and in vivo experiments demonstrated that the intercalated COF with D-A properties could effectively suppress the growth of tumors upon laser irradiation. This work provided a paradigm to feasibly construct D-A COF with promising photothermal performance for cancer treatment.

The combined plasma membrane coating and cluster bombing strategy for improved tumor-targeting gene delivery of silicon nanoclusters

With the promising biosafety and favorable cell imaging efficiency, silicon quantum dots (SiQDs) was broadly exploited as non-viral gene carriers in recent years. However, the low transfection efficiency and weak targeting ability hindered its further clinical applications. In this study, the combined plasma membrane coating and cluster bombing strategy was adopted to enhance the gene delivery potential of silicon quantum dots nanoclusters (SiNC). Initially, SiNC was generated via 3, 3′-Dithiodipropionic acid (DipA) crosslinking of SiQDs, then the obtained nanoclusters were coated by distinct plasma membrane. Interestingly, cell membrane coated SiNC (CM-SiNC) underwent particle size change, the typical character of “cluster bombing”, when exposed to high GSH concentration, which was observed in the tumor microenvironment. Meanwhile, CM-SiNC can be efficiently uptaken by HEK 293T and HeLa cells, therefore transferring DNA into those cells. More importantly, among the particles coated by HeLa (HeLa-M), Red Blood (RBC-M) or RAW267.4 (RAW-M) cell membrane, HeLa cell membrane coating exhibited better cellular uptake and transfection efficiency in HeLa cells, which suggested the encouraging tumor targeting ability. In sum, these data suggested that cluster bombing of SiNC could be beneficial for physical stability and biodistribution, the additional plasma membrane coating further endowed SiNC the efficient gene delivery and tumor targeting ability. Therefore, CM-SiNC had the potential as a gene delivery vector and its application should be further addressed in vivo.

Boosting nuclear-targeted photothermal-chemotherapy by NIR-responsive hybrid membrane camouflaged nanotherapeutics

BackgroundEngineering nanotherapeutics have been extensively studied for cancer therapy. However, the therapeutic efficacy is still severely restricted by biophysiological barriers and intracellular accumulation. Although the biomimetic nanoparticles have improved the former issue, there is almost no breakthrough in researches of intracellular transport. Herein, we proposed a NIR-responsive nuclear-targeted hybrid membrane biomimetic Prussian blue drug-loading nanotherapeutics (PB@DN@M).ResultsThe hybrid membrane coating bestows nanotherapeutics tumor targeting and immune escape ability, thus promoting the tumor enrichment of PB nanotherapeutics. The nuclear targeting function triggered by NIR enhances the cellular internalization and nuclear entry efficiency, resulting in a superadditive effect for boosting photothermal-chemotherapy efficacy. Moreover, taking advantage of non-interference Raman properties of PB, we can track the location and distribution of nanotherapeutics, which is beneficial for guiding precise synchronization of photothermal-chemotherapy. The results revealed that this PB@DN@M presented a remarkable therapeutic efficacy and significantly inhibited the tumor growth up to 87.17%.ConclusionsTherefore, this spatiotemporal controllable biomimetic nanotherapeutics will provide a new insight and strategy for specific targeted therapy of tumors.

Tumor-targeted liposomes with platycodin D2 promote apoptosis in colorectal cancer.

Conventional chemotherapy for colorectal cancer (CRC), though efficacious, is discouraging due to its limited targeting capability, lack of selectivity, and chemotherapy-associated side effects. With the advent of nanomedicines, a liposomal delivery system making use of a combination of anticancer phytochemicals is fast gaining popularity as one of the most promising nanoplatforms for CRC treatment. Rising evidence supports phytochemicals such as platycosides for their anticancer potency. To this end, a combination therapy including tumor-targeted liposomes along with phytochemicals might have a greater therapeutic potential against cancer. In this study, we developed acidity-triggered rational membrane (ATRAM) along with conjugated platycodin D2 (PCD2) and liposomes (PCD2-Lipo-ATRAM) as a tumor-targeting therapy. The PCD2-Lipo-ATRAM treatment demonstrated a successful tumor-targeting ability in the CRC xenografts, in which PCD2 not only exerted a potent antitumor effect by inducing apoptotic cell death and but also functioned as a liposome membrane stabilizer. Moreover, PCD2-Lipo-ATRAM suppressed antiapoptotic BCL-2 family proteins, resulting in enhanced cytotoxicity toward CRC cells by inducing intrinsic caspase-9/-3 mediated apoptosis. Thus, our data has shown that tumor-targeting PCD2-based liposomal systems represent a promising strategy for CRC therapy, since they directly target the tumors, unlike other therapies that can miss the target.