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1.
Energy metabolism abnormity is one of the most significant hallmarks of cancer. As a result, large amino acid transporter 1 (LAT1) is remarkably overexpressed in both blood‐brain‐barrier and glioma tumor cells, leading a rapid and sufficient substrate transportation. 3CDIT and 4CDIT are originally synthesized by modifying the existing most potent LAT1 substrate. 3CDIT is selected as its higher glioma‐targeting ability. Since the microenvironment variation in tumor cells is another important feature of cancer, a great disparity in adenosine‐5′‐triphosphate (ATP) and glutathione (GSH) levels between extracellular and intracellular milieu can provide good possibilities for dual‐responsive drug release in tumor cells. Doxorubicin (DOX) is successfully intercalated into the ATP aptamer DNA scaffolds, compressed by GSH‐responsive polymer pOEI, and modified with 3CDIT to obtain 3CDIT‐targeting pOEI/DOX/ATP aptamer nanoparticles (NPs). Enhanced NP accumulation and rapid GSH & ATP dual‐responsive DOX release in glioma are demonstrated both in vitro and in vivo. More efficient therapeutic effects are shown with 3CDIT‐targeting pOEI/DOX/ATP aptamer NPs than free DOX and no systemic toxicity is observed. Therefore, glioma‐targeting delivery and GSH & ATP dual‐responsive release guarantee an adequate DOX accumulation within tumor cells and ensure a safe and efficient chemotherapy for glioma.  相似文献   

2.
Multidrug resistance (MDR) remains one of the biggest obstacles in chemotherapy of tumor mainly due to P‐glycoprotein (P‐gp)‐mediated drug efflux. Here, a transformable chimeric peptide is designed to target and self‐assemble on cell membrane for encapsulating cells and overcoming tumor MDR. This chimeric peptide (C16‐K(TPE)‐GGGH‐GFLGK‐PEG8, denoted as CTGP) with cathepsin B‐responsive and cell membrane‐targeting abilities can self‐assemble into nanomicelles and further encapsulate the therapeutic agent doxorubicin (termed as CTGP@DOX). After the cleavage of the Gly‐Phe‐Leu‐Gly (GFLG) sequence by pericellular overexpressed cathepsin B, CTGP@DOX is dissociated and transformed from spherical nanoparticles to nanofibers due to the hydrophilic–hydrophobic conversion and hydrogen bonding interactions. Thus obtained nanofibers with cell membrane‐targeting 16‐carbon alkyl chains can adhere firmly to the cell membrane for cell encapsulation and restricting DOX efflux. In comparison to free DOX, 45‐time higher drug retention and 49‐fold greater anti‐MDR ability of CTGP@DOX to drug‐resistant MCF‐7R cells are achieved. This novel strategy to encapsulate cells and reverse tumor MDR via morphology transformation would open a new avenue towards chemotherapy of tumor.  相似文献   

3.
Multidrug resistance (MDR) and adverse side effects are the major challenges facing cancer chemotherapy. Here, pH/protease dually responsive, sericin‐coated mesoporous silica nanoparticles (SMSNs) for lysosomal delivery of doxorubicin (DOX) to overcome MDR and reduce systemic toxicity are reported. Sericin, a natural protein from silkworm cocoons, is coated onto MSNs as a gatekeeper via pH sensitive imine linkages. The sericin shell prevents the premature leakage of encapsulated DOX from MSNs in extracellular environment. Once reaching drug‐resistant tumors, sericin's cell‐adhesive bioactivity enhances cellular uptake of SMSNs that are in turn transported into perinuclear lysosomes, thus avoiding drug efflux mediated by membrane‐bound pumps. Lysosomal acidity triggers cleavage of pH sensitive linkage between sericin and MSNs concurrently with lysosomal proteases deconstructing sericin shell. This pH/protease dual responsiveness leads to DOX burst release into cell nuclei, inducing effective cell death, thus reversing MDR. These DOX‐loaded SMSNs not only effectively kill drug‐resistant cells in vitro, but also significantly reduce the growth of DOX‐resistant MCF‐7/ADR (breast cancer cells) tumor by 70% in a preclinical animal model without eliciting systemic toxicity frequently encountered in current clinical therapeutic formulations. Thus, the dually responsive SMSNs are an effective, lysosome‐tropic, and bio‐safe delivery system for chemotherapeutics for combating MDR.  相似文献   

4.
Insufficient drug release as well as poor drug penetration are major obstacles for effective nanoparticles (NPs)‐based cancer therapy. Herein, the high aqueous instability of amorphous calcium carbonate (ACC) is employed to construct doxorubicin (DOX) preloaded and monostearin (MS) coated “Pandora's box” (MS/ACC–DOX) NPs for lipase‐triggered water‐responsive drug release in lipase‐overexpressed tumor tissue to induce a neighboring effect and enhance drug penetration. MS as a solid lipid can prevent potential drug leakage of ACC–DOX NPs during the circulatory process, while it can be readily be disintegrated in lipase‐overexpressed SKOV3 cells to expose the ACC–DOX core. The high aqueous instability of ACC will lead to burst release of the encapsulated DOX to induce apoptosis and cytotoxicity to kill the tumor cells. The liberated NPs from the dead or dying cells continue to respond to the ubiquitous aqueous environment to sufficiently release DOX once unpacked, like the “Pandora's box”, leading to severe cytotoxicity to neighboring cells (neighboring effect). Moreover, the continuously released free DOX molecules can readily diffused through the tumor extracellular matrix to enhance drug penetration to deep tumor tissue. Both effects contribute to achieve elevated antitumor benefits.  相似文献   

5.
Despite the exciting advances in cancer chemotherapy over past decades, drug resistance in cancer treatment remains one of the primary reasons for therapeutic failure. IR‐780 loaded pH‐responsive polymeric prodrug micelles with near infrared (NIR) photothermal effect are developed to circumvent the drug resistance in cancer treatment. The polymeric prodrug micelles are stable in physiological environment, while exhibit fast doxorubicin (DOX) release in acidic condition and significant temperature elevation under NIR laser irradiation. Phosphorylcholine‐based biomimetic micellar shell and acid‐sensitive drug conjugation endow them with prolonged circulation time and reduced premature drug release during circulation to conduct tumor site‐specific chemotherapy. The polymeric prodrug micelles combined with NIR laser irradiation could significantly enhance intracellular DOX accumulation and synergistically induce the cell apoptosis in DOX‐resistant MCF‐7/ADR cells. Meanwhile, the tumor site‐specific chemotherapy combined with hyperthermia effect induces significant inhibition of MCF‐7/ADR tumor growth in tumor‐bearing mice. These results demonstrate that the well‐designed IR‐780 loaded polymeric prodrug micelles for hyperthermia‐assisted site‐specific chemotherapy present an effective approach to reverse drug resistance.  相似文献   

6.
You J  Hu FQ  Du YZ  Yuan H 《Nanotechnology》2008,19(25):255103
For antitumor drugs with an intracellular action site in the nucleus, effective internalization of the drugs into cancer cells and accumulation in the nucleus should be the determinant step for high antitumor activity. We synthesized a novel chitosan derivative by grafting stearic acid onto chitosan. The derivative can form self-aggregated micelles with about 50?nm size in the aqueous medium, and then can load a poorly soluble antitumor drug (doxorubicin, DOX) with high entrapment efficiency and drug loading. DOX release from the micelles was retarded significantly as a result of the encapsulation of the micelles. DOX concentration in nuclei was increased significantly via the transport of the micelles. Consequently, cytotoxicity of DOX loaded micelles was improved sharply due to the accumulation of the drug in its intracellular action site. The present micelles are a promising carrier candidate for effective therapy of antitumor drugs with the action site in the nucleus.  相似文献   

7.
Combination chemotherapy with time‐programmed administration of multiple drugs is a promising method for cancer treatment. However, realizing time‐programmed release of combined drugs from a single carrier is still a great challenge in enhanced cancer therapy. Here, an implantable trilayer structured fiber device is developed to achieve time‐programmed release of combined drugs for synergistic treatment of breast cancer. The fiber device is prepared by a modified microfluidic‐electrospinning technique. The glycerol solution containing chemotherapy agent doxorubicin (Dox) forms the internal periodic cavities of the fiber, and poly(l ‐lactic acid) and poly(ε‐caprolactone) containing the angiogenesis inhibitor apatinib (Apa) form the double walls of the fiber. Rapid release of Dox can be obtained by adjusting the wall thickness of the cavities, meanwhile sustained release of Apa is achieved through the slow degradation of the fiber matrix. After the fiber device is implanted subcutaneously near to the implanted solid tumor of mice, an excellent synergistic therapeutic effect is achieved through time‐programmed release of the combined dual drugs. The fiber device provides a platform to sequentially co‐deliver dual or multiple drugs for enhanced combined therapeutic efficacy.  相似文献   

8.
Nanomedicine to overcome both systemic and tumor tissue barriers ideally should have a transformable size and surface, maintaining a certain size and negative surface charge for prolonged circulation, while reducing to a smaller size and switching to a positive surface charge for efficient penetration to and retention in the interstitial space throughout the tumor tissue. However, the design of such size and charge dual‐transformable nanomedicine is rarely reported. Here, the design of a shell‐stacked nanoparticle (SNP) is reported, which can undergo remarkable size reduction from about 145 to 40 nm, and surface charge reversal from ?7.4 to 8.2 mV at acidic tumor tissue, for enhanced tumor penetration and uptake by cells in deep tumor tissue. The disulfide‐cross‐linked core maintains the stability of the particle and prevents undesired premature drug release until the shedding of the shell, which accelerates the cleavage of more exposed disulfide bond sand intracellular drug release. SNP penetrates about 1 mm into xenografted A549 lung carcinoma, which is about four times penetration depth of the nontransformable one. The doxorubicin (DOX)‐loaded SNP (SNP/DOX) shows significant antitumor efficacy and nearly eradicates the tumor, substantiating the importance of the design of size and charge dual‐transformable nanomedicine.  相似文献   

9.
Multidrug resistance (MDR) is a major obstacle to the effective chemotherapy in many human malignancies. Nanoparticulate drug delivery systems (NDDSs) have been reported to be able to bypass MDR, but the cancer therapeutic efficacy is still limited. In this study, we firstly designed the nonspherical mesoporous silica nanorods (MSNRs) with aspect ratio (AR) of 1.5 and 5 as drug delivery systems of doxorubicin to overcome multidrug resistance. For drug loading, the long-rod MSNRs (NLR, AR = 5) showed higher drug loading capacity of doxorubicin (DOX) than the short-rod MSNRs (NSR, AR = 1.5). NLR encapsulated DOX had increased intracellular DOX accumulation in drug-resistant Chinese hamster ovary (CHO) cells compared with free DOX by observablly increased cellular uptake and significantly prolonged intracellular drug retention. It further exhibited increased cytotoxicity compared with free DOX under different drug concentrations. These findings may provide a new perspective for designing high-performance nanoparticulate drug delivery systems for bypassing multidrug resistance of cancer therapy.  相似文献   

10.
Responsive nanomaterials have emerged as promising candidates as drug delivery vehicles in order to address biomedical diseases such as cancer. In this work, polymer‐based responsive nanoparticles prepared by a supramolecular approach are loaded with doxorubicin (DOX) for the cancer therapy. The nanoparticles contain disulfide bonds within the polymer network, allowing the release of the DOX payload in a reducing environment within the endoplasm of cancer cells. In addition, the loaded drug can also be released under acidic environment. In vitro anticancer studies using redox and pH dual responsive nanoparticles show excellent performance in inducing cell death and apoptosis. Zebrafish larvae treated with DOX‐loaded nanoparticles exhibit an improved viability as compared with the cases treated with free DOX by the end of a 3 d treatment. Confocal imaging is utilized to provide the daily assessment of tumor size on zebrafish larva models treated with DOX‐loaded nanoparticles, presenting sustainable reduction of tumor. This work demonstrates the development of functional nanoparticles with dual responsive properties for both in vitro and in vivo drug delivery in the cancer therapy.  相似文献   

11.
Drug resistance is the greatest challenge in clinical cancer chemotherapy. Co‐delivery of chemotherapeutic drugs and siRNA to tumor cells is a vital means to silence drug resistant genes during the course of cancer chemotherapy for an improved chemotherapeutic effect. This study aims at effective co‐delivery of siRNA and anticancer drugs to tumor cells. A ternary block copolymer PEG‐PAsp(AED)‐PDPA consisting of pH‐sensitive poly(2‐(diisopropyl amino)ethyl methacrylate) (PDPA), reduction‐sensitive poly(N‐(2,2′‐dithiobis(ethylamine)) aspartamide) PAsp(AED), and poly(ethylene glycol) (PEG) is synthesized and assembled into a core‐shell structural micelle which encapsulated doxorubicin (DOX) in its pH‐sensitive core and the siRNA‐targeting anti‐apoptosis BCL‐2 gene (BCL‐2 siRNA) in a reduction‐sensitive interlayer. At the optimized size and zeta potential, the nanocarriers loaded with DOX and BCL‐2 siRNA may effectively accumulate in the tumor site via blood circulation. Moreover, the dual stimuli‐responsive design of micellar carriers allows microenviroment‐specific rapid release of both DOX and BCL‐2 siRNA inside acidic lysosomes with enriched reducing agent, glutathione (GSH, up to 10 mm ). Consequently, the expression of anti‐apoptotic BCL‐2 protein induced by DOX treatment is significantly down‐regulated, which results in synergistically enhanced apoptosis of human ovarian cancer SKOV‐3 cells and thus dramatically inhibited tumor growth.  相似文献   

12.
Nanodrug‐based cancer therapy is impeded by poor penetration into deep tumor tissues mainly due to the overexpression of hyaluronic acid (HA) in the tumor extracellular matrix (ECM). Although modification of nanoparticles (NPs) with hyaluronidase (HAase) is a potent strategy, it remains challenging to get a uniform distribution of drug at the tumor site because of the internalization of NPs by the cells in the tumor and HA regeneration. Herein, an intelligent nanocarrier, which can release HAase in response to the acidic tumor microenvironment (pH 6.5) and perform a strong neighboring effect with size reduction to overcome the above two problems and accomplish drug deep tumor penetration in vivo, is reported. In this design, HAase is encapsulated on the surfaces of doxorubicin (DOX) preloaded ZnO‐DOX NPs using a charge convertible polymer PEG‐PAH‐DMMA (ZDHD). The polymer can release HAase to degrade HA in the tumor ECM (pH 6.5). ZnO‐DOX NPs can release DOX in lysosomes (pH 4.5) to induce cell apoptosis, and exert a neighboring effect with size reduction to infect neighboring cells. The hierarchical targeted release of HAase and drugs is demonstrated to enhance tumor penetration and decrease side effects in vivo. This work shows promise for further application of ZDHD NPs in cancer therapy.  相似文献   

13.
Prodrug therapy is one strategy to deliver anticancer drugs in a less reactive manner to reduce nonspecific cytotoxicity. A new multifunctional anticancer prodrug system based on water‐dispersible fullerene (C60) aggregates is introduced; this prodrug system demonstrates active targeting, pH‐responsive chemotherapy, and photodynamic therapeutic (PDT) properties. Incorporating (via a cleavable bond) an anticancer drug, which is doxorubicin (DOX) in this study, and a targeting ligand (folic acid) onto fullerene while maintaining an overall size of approximately 135 nm produces a more specific anticancer prodrug. This prodrug can enter folate receptor (FR)‐positive cancer cells and kill the cells via intracellular release of the active drug form. Moreover, the fullerene aggregate carrier exhibits PDT action; the cytotoxicity of the system towards FR‐positive cancer cells is increased in response to light irradiation. As the DOX drug molecules are conjugated onto fullerene, the DOX fluorescence is significantly quenched by the strong electron‐accepting capability of fullerene. The fluorescence restores upon release from fullerene, so this fluorescence quenching–restoring feature can be used to track intracellular DOX release. The combined effect of chemotherapy and PDT increases the therapeutic efficacy of the DOX–fullerene aggregate prodrug. This study provides useful insights into designing and improving the applicability of fullerene for other targeted cancer prodrug systems.  相似文献   

14.
A cascade amplification release nanoparticle (CARN) is constructed by the coencapsulation of β‐lapachone and a reactive‐oxygen‐species (ROS)‐responsive doxorubicin (DOX) prodrug, BDOX, in polymeric nanoparticles. Releasing β‐lapachone first from the CARNs selectively increases the ROS level in cancer cells via NAD(P)H:quinone oxidoreductase‐1 (NQO1) catalysis, which induces the cascade amplification release of DOX and overcomes multidrug resistance (MDR) in cancer cells, producing a remarkably improved therapeutic efficacy against MDR tumors with minimal side effects.  相似文献   

15.
A novel type of nanovehicle (NV) based on stimuli‐responsive supramolecular peptide‐amphiphiles (SPAs, dendritic poly (L‐lysine) non‐covalently linked poly (L‐leucine)) is developed for intracellular drug delivery. To determine the pH‐dependent mechanism, the supramolecular peptide‐amphiphile system (SPAS) is investigated at different pH conditions using a variety of physical and chemical approaches. The pH‐triggered disassembly of SPAS can be attributed to the disappearance of non‐covalent interactions within SPAs around the isoelectric point of poly (L‐leucine). SPAS is found to encapsulate guest molecules at pH 7.4 but release them at pH 6.2. In this way, SPAS is able to act as a smart NV to deliver its target to tumor cells using intracellular pH as a trigger. The DOX‐loaded NVs are approximately 150 nm in size. In vitro release profiles and confocal laser scanning microscopy (CLSM) images of HepG2 cells confirm that lower pH conditions can trigger the disassembly of NVs and so achieve pH‐dependent intracellular DOX delivery. In vitro cytotoxicity of the DOX‐loaded NVs to HepG2 cells demonstrate that the smart NVs enhance the efficacy of hydrophobic DOX. Fluorescence‐activated cell sorting (FACS) and CLSM results show that the NVs can enhance the endocytosis of DOX into HepG2 cells considerably and deliver DOX to the nuclei.  相似文献   

16.
Smart nanoparticles are increasingly important in a variety of applications such as cancer therapy. However, it is still a major challenge to develop light‐responsive nanoparticles that can maximize the potency of synergistic thermo‐chemotherapy under light irradiation. Here, spatially confined cyanine‐anchored silica nanochannels loaded with chemotherapeutic doxorubicin (CS‐DOX‐NCs) for light‐driven synergistic cancer therapy are introduced. CS‐DOX‐NCs possess a J‐type aggregation conformation of cyanine dye within the nanochannels and encapsulate doxorubicin through the π–π interaction with cyanine dye. Under near‐infrared light irradiation, CS‐DOX‐NCs produce the enhanced photothermal conversion efficiency through the maximized nonradiative transition of J‐type Cypate aggregates, trigger the light‐driven drug release through the destabilization of temperature‐sensitive π–π interaction, and generate the effective intracellular translocation of doxorubicin from the lysosomes to cytoplasma through reactive oxygen species‐mediated lysosomal disruption, thereby causing the potent in vivo hyperthermia and intracellular trafficking of drug into cytoplasma at tumors. Moreover, CS‐DOX‐NCs possess good resistance to photobleaching and preferable tumor accumulation, facilitating severe photoinduced cell damage, and subsequent synergy between photothermal and chemotherapeutic therapy with tumor ablation. These findings provide new insights of light‐driven nanoparticles for synergistic cancer therapy.  相似文献   

17.
Chemotherapy is well recognized to induce immune responses during some chemotherapeutic drugs‐mediated tumor eradication. Here, a strategy involving blocking programmed cell death protein 1 (PD‐1) to enhance the chemotherapeutic effect of a doxorubicin nanoprodrug HA‐Psi‐DOX is proposed and the synergetic mechanism between them is further studied. The nanoprodrugs are fabricated by conjugating doxorubicin (DOX) to an anionic polymer hyaluronic acid (HA) via a tumor overexpressed matrix metalloproteinase sensitive peptide (CPLGLAGG) for tumor targeting and enzyme‐activated drug release. Once accumulated at the tumor site, the nanoprodrug can be activated to release antitumor drug by tumor overexpressed MMP‐2. It is found that HA‐Psi‐DOX nanoparticles can kill tumor cells effectively and initiate an antitumor immune response, leading to the upregulation of interferon‐γ. This cytokine promotes the expression of programmed cell death protein‐ligand 1 (PD‐L1) on tumor cells, which will cause immunosuppression after interacting with PD‐1 on the surface of lymphocytes. The results suggest that the therapeutic efficiency of HA‐Psi‐DOX nanoparticles is significantly improved when combined with checkpoint inhibitors anti‐PD‐1 antibody (α‐PD1) due to the neutralization of immunosuppression by blocking the interaction between PD‐L1 and PD‐1. This therapeutic system by combining chemotherapy and immunotherapy further increases the link between conventional tumor therapies and immunotherapy.  相似文献   

18.
Nanomedicine (NM) cannot penetrate deeply into solid tumors, which is partly attributed to the heterogeneous microenvironment and high interstitial fluid pressure of solid tumors. To improve NM efficacy, there has been tremendous effort developing tumor‐penetrating NMs by miniaturizing NM sizes or controlling NM surface properties. But progress along the direction of developing tumor penetrating nanoparticle has been slow and improvement of the overall antitumor efficacy has been limited. Herein, a novel strategy of inhibiting solid tumor with high efficiency by dual‐functional, nontumor‐penetrating NM is demonstrated. The intended NM contains 5,6‐dimethylxanthenone‐4‐acetic acid (DMXAA), a vascular‐disrupting agent, and doxorubicin (DOX), a cytotoxic drug. Upon arriving at the target tumor site, sustained release of DMXAA from NMs results in disruption of tumor vessel functions, greatly inhibiting the interior tumor cells by cutting off nutritional supply. Meanwhile, the released DOX kills the residual cells at the tumor exterior regions. The in vivo studies demonstrate that this dual‐functional, nontumor penetrating NM exhibits superior anticancer activity, revealing an alternative strategy of effective tumor growth inhibition.  相似文献   

19.
Light‐triggered drug delivery based on near‐infrared (NIR)‐mediated photothermal nanocarriers has received tremendous attention for the construction of cooperative therapeutic systems in nanomedicine. Herein, a new paradigm of light‐responsive drug carrier that doubles as a photothermal agent is reported based on the NIR light‐absorber, Rb x WO3 (rubidium tungsten bronze, Rb‐TB) nanorods. With doxorubicin (DOX) payload, the DOX‐loaded Rb‐TB composite (Rb‐TB‐DOX) simultaneously provides a burst‐like drug release and intense heating effect upon 808‐nm NIR light exposure. MTT assays show the photothermally enhanced antitumor activity of Rb‐TB‐DOX to the MCF‐7 cancer cells. Most remarkably, Rb‐TB‐DOX combined with NIR irradiation also shows dramatically enhanced chemotherapeutic effect to DOX‐resistant MCF‐7 cells compared with free DOX, demonstrating the enhanced efficacy of combinational chemo‐photothermal therapy for potentially overcoming drug resistance in cancer chemotherapy. Furthermore, in vivo study of combined chemo‐photothermal therapy is also conducted and realized on pancreatic (Pance‐1) tumor‐bearing nude mice. Apart from its promise for cancer therapy, the as‐prepared Rb‐TB can also be employed as a new dual‐modal contrast agent for photoacoustic tomography and (PAT) X‐ray computed tomography (CT) imaging because of its high NIR optical absorption capability and strong X‐ray attenuation ability, respectively. The results presented in the current study suggest promise of the multifunctional Rb x WO3 nanorods for applications in cancer theranostics.  相似文献   

20.
The use of biodegradable polymeric nanoparticles (NPs) for controlled drug delivery has shown significant therapeutic potential. Polyaspartic acid and polylactic acid are the most intensively studied biodegradable polymers. In the present study, novel amphiphilic biodegradable co-polymer NPs, poly(L-aspartic acid-co-lactic acid) with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) (poly(AA-co-LA)/DPPE) is synthesized and subsequently used to encapsulate an antitumor drug doxorubicin (DOX). The formulation parameters of the NPs are optimized to improve encapsulation efficiency. The resulting drug-loaded NPs possess better size homogeneity (polydispersity) and exhibit pH-responsive drug release profiles. Cellular viability assays indicate that the poly(AA-co-LA)/DPPE NPs did not induce cell death, whereas doxorubicin encapsulated NPs were cytotoxic to various types of tumor cells. In addition, the free NPs could not enter the cell nuclei after internalized in tumor cells. The DOX-loaded NPs exhibit efficient intracellular delivery in tumor cells with co-localization in lysosome and delay entering into the nucleus, which suggests a time- and pH-dependent drug release profile within cells. When applied to deliver chemotherapeutics to a mouse xenograft model of human lung adenocarcinoma, DOX-loaded NPs have a comparable antitumor activity with free DOX, and greatly reduce systemic toxicity and mortality. The delivery of cytotoxic drugs directly to the nucleus specifically within tumor cells is of great interest. These results demonstrate the feasibility of the application of the amphiphilic polyaspartic acid derivative, poly(AA-co-LA)/DPPE, as a nanocarrier for cell nuclear delivery of potent antitumor drugs.  相似文献   

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