Peptide-functionalized therapeutic nanoplatform for treatment orthotopic triple negative breast cancer and bone metastasis.

Epidermal Growth Factor Receptor (EGFR) is a promising therapeutic target for triple-negative breast cancer (TNBC). Recently, specific EGFR-targeting peptide GE11-based delivery nano-system shows excellent potential because of its chemical versatility and good targeting ability. However, no further research focusing on the downstream of EGFR after binding with GE11 was explored. Hence, we tailor-designed a self-assembled nanoplatform named GENP using amphiphilic molecule of stearic acid-modified GE11. After loading doxorubicin (DOX), the resulted nanoplatform GENP@DOX demonstrated high loading efficiency and sustainable drug release. Importantly, our findings proved that GENP alone significantly suppressed the proliferation of MDA-MB-231 cells via EGFR-downstream PI3K/AKT signaling pathways, contributing to the synergistic treatment with its DOX release. Further work illustrated remarkable therapeutic efficacy both in orthotopic TNBC and its bone metastasis models with minimal biotoxicity. Together, the results highlight that our GENP-functionalized nanoplatform is a promising strategy for the synergistic therapeutic efficacy targeting EGFR-overexpressed cancer.

Self-assembled peptide hydrogel scaffolds with VEGF and BMP-2 enhanced in vitro angiogenesis and osteogenesis.

OBJECTIVES: The reconstruction of bone defects remains a major clinical issue. Our study aims to investigate the ability of RATEA16 (RA, [CH3CONH] RADARADARADARADA-[CONH2]) for the sustained delivering VEGF and BMP-2 to promote angiogenesis and osteogenesis in bone reconstruction. MATERIALS AND METHODS: We prepared and investigated the characterization of RATEA16. The survival of human umbilical vein endothelial cells (HUVECs) and human stem cells of the apical papilla (SCAPs) encapsulated in RATEA16 hydrogel was detected. Then, we established RA-VEGF/BMP-2 drug delivery systems and measured their drug release pattern. The effects of RA-VEGF scaffolds on HUVECs angiogenesis were investigated in vitro. Then, osteoblastic differentiation capacity of SCAPs with RA-BMP-2 scaffolds was analyzed by ALP activity and expression of osteoblast-related genes. RESULTS: A porous nanofiber microstructure endowed this scaffold with the ability to maintain the survival of HUVECs and SCAPs. The RA-VEGF/BMP-2 drug delivery systems exhibited several advantagesin vitro: injectability, biodegradability, good biocompatibility, and noncytotoxicity. Released rhVEGF165 /BMP-2 were proved to promote angiogenesis of HUVECs as well as osteogenesis of SCAPs abilities. CONCLUSION: RATEA16 loading with VEGF and BMP-2 might be a potential clinical strategy for tissue engineering, especially in bone reconstruction, due to its ability of delivering growth factors effectively and efficiently.

Discovery of N-aryl sulphonamide-quinazoline derivatives as anti-gastric cancer agents in vitro and in vivo via activating the Hippo signalling pathway.

Hippo signalling pathway plays a crucial role in tumorigenesis and cancer progression. In this work, we identified an N-aryl sulphonamide-quinazoline derivative, compound 9i as an anti-gastric cancer agent, which exhibited potent antiproliferative ability with IC50 values of 0.36 µM (MGC-803 cells), 0.70 µM (HCT-116 cells), 1.04 µM (PC-3 cells), and 0.81 µM (MCF-7 cells), respectively and inhibited YAP activity by the activation of p-LATS. Compound 9i was effective in suppressing MGC-803 xenograft tumour growth in nude mice without obvious toxicity and significantly down-regulated the expression of YAP in vivo. Compound 9i arrested cells in the G2/M phase, induced intrinsic apoptosis, and inhibited cell colony formation in MGC-803 and SGC-7901 cells. Therefore, compound 9i is to be reported as an anti-gastric cancer agent via activating the Hippo signalling pathway and might help foster a new strategy for the cancer treatment by activating the Hippo signalling pathway regulatory function to inhibit the activity of YAP.

Tumor-Specific Silencing of Tissue Factor Suppresses Metastasis and Prevents Cancer-Associated Hypercoagulability.

Within tumors, the coagulation-inducing protein tissue factor (TF), a major initiator of blood coagulation, has been shown to play a critical role in the hematogenous metastasis of tumors, due to its effects on tumor hypercoagulability and on the mediation of interactions between platelets and tumor cells. Targeting tumor-associated TF has therefore great therapeutic potential for antimetastasis therapy and preventing thrombotic complication in cancer patients. Herein, we reported a novel peptide-based nanoparticle that targets delivery and release of small interfering RNA (siRNA) into the tumor site to silence the expression of tumor-associated TF. We showed that suppression of TF expression in tumor cells blocks platelet adhesion surrounding tumor cells in vitro. The downregulation of TF expression in intravenously administered tumor cells (i.e., simulated circulating tumor cells [CTCs]) prevented platelet adhesion around CTCs and decreased CTCs survival in the lung. In a breast cancer mouse model, siRNA-containing nanoparticles efficiently attenuated TF expression in the tumor microenvironment and remarkably reduced the amount of lung metastases in both an experimental lung metastasis model and tumor-bearing mice. What's more, this strategy reversed the hypercoagulable state of the tumor bearing mice by decreasing the generation of thrombin-antithrombin complexes (TAT) and activated platelets, both of which are downstream products of TF. Our study describes a promising approach to combat metastasis and prevent cancer-associated thrombosis, which advances TF as a therapeutic target toward clinic applications.

Restoration of Sinusoid Fenestrae Followed by Targeted Nanoassembly Delivery of an Anti-Fibrotic Agent Improves Treatment Efficacy in Liver Fibrosis.

During the onset of liver fibrosis, capillarized liver sinusoidal endothelial cells (LSECs) limit substance exchange between the blood and the Disse space, further accelerating hepatic stellate cell (HSCs) activation and fibrosis progression. Limited accessibility of therapeutics to the Disse space is often overlooked and remains a major bottleneck for HSCs-targeted therapy in liver fibrosis. Here, an integrated systemic strategy for liver fibrosis treatment is reported, utilizing pretreatment with the soluble guanylate cyclase stimulator, riociguat, followed by insulin growth factor 2 receptor-mediated targeted delivery of the anti-fibrosis agent, JQ1, via peptide-nanoparticles (IGNP-JQ1). The riociguat reversed the liver sinusoid capillarization to maintain a relatively normal LSECs porosity, thus facilitating the transport of IGNP-JQ1 through the liver sinusoid endothelium wall and enhancing the accumulation of IGNP-JQ1 in the Disse space. IGNP-JQ1 is then selectively taken up by activated HSCs, inhibiting their proliferation and decreasing collagen deposition in the liver. The combined strategy results in significant fibrosis resolution in carbon tetrachloride-induced fibrotic mice as well as methionine-choline-deficient-diet-induced nonalcoholic steatohepatitis (NASH) mice. The work highlights the key role of LSECs in therapeutics transport through the liver sinusoid. The strategy of restoring LSECs fenestrae by riociguat represents a promising approach for liver fibrosis treatment.

Discovery of novel coumarin-indole derivatives as tubulin polymerization inhibitors with potent anti-gastric cancer activities.

Novel coumarin-indole derivatives were designed, synthesized and evaluated as tubulin polymerization inhibitors targeting the colchicine binding site. Among these compounds, compound MY-413 displayed the most potent inhibitory activities against gastric cancer cell line MGC-803 with an IC50 value of 0.011 µM. Furthermore, the IC50 values of compound MY-413 was less than 0.1 µM for other 17 cancer cell lines and less than 0.05 µM for other 8 cancer cell lines. Compound MY-413 effectively inhibited the tubulin polymerization (IC50 = 2.46 µM) by binding to the colchicine site. Screening for the inhibitory effects of compound MY-413 on 61 kinases, it was found that compound MY-413 could inhibit MAPK pathways-related kinases. Because of the inhibitory effects of compound MY-413 on tubulin polymerization and MAPK signaling pathway, compound MY-413 induced cell apoptosis, arrested the cell cycle in the G2/M phase, induced the inhibition of cell proliferation and migration in gastric cancer cells MGC-803 and HGC-27. In addition, compound MY-413 could significantly inhibit tumor growth in MGC-803 xenograft tumor models with tumor growth inhibition (TGI) rates of 70% (15 mg/kg) and 80% (30 mg/kg) without obvious toxicity. Consistent with the in vitro results, compound MY-413 also inhibited MAPK signaling pathway, and induced apoptosis and proliferation inhibition in vivo. In conclusion, this work indicated that compound MY-413 was a promising lead compound for the further investigation as a potential anti-gastric cancer agent.

Bifunctional Therapeutic Peptide Assembled Nanoparticles Exerting Improved Activities of Tumor Vessel Normalization and Immune Checkpoint Inhibition.

The effectiveness of cancer immunotherapy is impaired by the dysfunctional vasculature of tumors. Created hypoxia zones and limited delivery of cytotoxic immune cells help to have immune resistance in tumor tissue. Structural and functional normalization of abnormal tumor vasculature provide vessels for more perfusion efficiency and drug delivery that result in alleviating the hypoxia in the tumor site and increasing infiltration of antitumor T cells. Taking advantage of peptide amphiphiles, herein, a novel peptide amphiphile nanoparticle composed of an antiangiogenic peptide (FSEC) and an immune checkpoint blocking peptide (D PPA) is designed and characterized. FSEC peptide is known to be involved in vessel normalization of tumors in vivo. D PPA is an inhibitory peptide of the PD-1/PD-L1 immune checkpoint pathway. The peptide amphiphile nanoparticle sets out to test whether simultaneous modulation of tumor vasculature and immune systems in the tumor microenvironment has a synergistic effect on tumor suppression. Increased intratumoral infiltration of immune cells following vascular normalization, and simultaneously blocking the immune checkpoint function of PD-L1 reactivates effective immune responses to the tumors. In summary, the current study provides a new perspective on the regulation of tumor vessel normalization and immunotherapy based on functional peptide nanoparticles as nanomedicine for improved therapeutic purposes.

Bioengineered bacteria-derived outer membrane vesicles as a versatile antigen display platform for tumor vaccination via Plug-and-Display technology.

An effective tumor vaccine vector that can rapidly display neoantigens is urgently needed. Outer membrane vesicles (OMVs) can strongly activate the innate immune system and are qualified as immunoadjuvants. Here, we describe a versatile OMV-based vaccine platform to elicit a specific anti-tumor immune response via specifically presenting antigens onto OMV surface. We first display tumor antigens on the OMVs surface by fusing with ClyA protein, and then simplify the antigen display process by employing a Plug-and-Display system comprising the tag/catcher protein pairs. OMVs decorated with different protein catchers can simultaneously display multiple, distinct tumor antigens to elicit a synergistic antitumour immune response. In addition, the bioengineered OMVs loaded with different tumor antigens can abrogate lung melanoma metastasis and inhibit subcutaneous colorectal cancer growth. The ability of the bioengineered OMV-based platform to rapidly and simultaneously display antigens may facilitate the development of these agents for personalized tumour vaccines.

A Graphdiyne Oxide-Based Iron Sponge with Photothermally Enhanced Tumor-Specific Fenton Chemistry.

Fenton reaction-mediated oncotherapy is an emerging strategy which uses iron ions to catalytically convert endogenous hydrogen peroxide into hydroxyl radicals, the most reactive oxygen species found in biology, for efficient cancer therapy. However, Fenton reaction efficiency in tumor tissue is typically limited due to restrictive conditions. One strategy to overcome this obstacle is to increase the temperature specifically at the tumor site. Herein, a tumor-targeting iron sponge (TTIS) nanocomposite based on graphdiyne oxide, which has a high affinity for iron is described. TTIS can accumulate in tumor tissue by decoration with a tumor-targeting polymer to enable tumor photoacoustic and magnetic resonance imaging. With its excellent photothermal conversion efficiency (37.5%), TTIS is an efficient photothermal therapy (PTT) agent. Moreover, the heat produced in the process of PTT can accelerate the release of iron ions from TTIS and simultaneously enhance the efficiency of the Fenton reaction, thus achieving a combined PTT and Fenton reaction-mediated cancer therapy. This work introduces a graphdiyne oxide-based iron sponge that exerts an enhanced antitumor effect through PTT and Fenton chemistry.

Dual-Antigen-Loaded Hepatitis B Virus Core Antigen Virus-like Particles Stimulate Efficient Immunotherapy Against Melanoma.

Tumor cells are rich in antigens, which provide a reliable antigen library for the design of personalized vaccines. However, an effective tumor vaccine vector that can efficiently deliver antigens to lymphoid organs to stimulate strong CD8+ cytotoxic T-lymphocyte immune response is still lacking. Here we designed a dual-antigen delivery system based on hepatitis B virus core antigen virus-like particles (HBc VLPs). We first confirmed that different antigen-loaded HBc VLP monomers could be assembled into nanoparticles (hybrid VLPs). Hybrid VLPs could slightly enhance bone marrow-derived dendritic cell maturation in vitro. Strikingly, hybrid VLPs could generate antigen-specific antitumor immunity and innate immunity in vivo which could significantly inhibit tumor growth or metastatic formation in a subcutaneous tumor or lung metastatic tumor model, respectively. Moreover, dual-epitope vaccination generated enhanced T-cell responses that potently inhibited tumor growth and metastatic formation. Together, this study provides a new powerful concept for cancer immunotherapy and suggests a novel design for VLP-based personalized nanomedicine.

Reshaping Prostate Tumor Microenvironment To Suppress Metastasis via Cancer-Associated Fibroblast Inactivation with Peptide-Assembly-Based Nanosystem.

Prostate cancer is one of the most common malignant tumors in men, and inhibiting metastasis is a key event but still a major challenge in prostate cancer treatment. Cancer-associated fibroblasts (CAFs) play an important role in prostate tumor metastasis by shaping the malignant tumor microenvironment. Herein, we constructed a CAF-targeting siRNA delivery system by loading the fibroblast activation protein-α (FAP-α) antibody onto the cell-penetrating peptide (CPP)-based nanoparticles, which specifically downregulated C-X-C motif chemokine ligand 12 (CXCL12) expression in CAFs. This regulation generated a series of changes through inactivating CAFs so that the malignant prostate tumor microenvironment was reshaped. The tumor cell invasion, migration, and tumor angiogenesis were significantly inhibited, which all contributed to the suppression of the metastasis of an orthotopic prostate tumor. This tumor microenvironment reshaping strategy via CAF targeting and inactivation provides an alternative approach for malignant prostate tumor metastasis inhibition.

Sulforaphane Mediates Glutathione Depletion via Polymeric Nanoparticles to Restore Cisplatin Chemosensitivity.

Platinum (Pt)-based chemotherapy is a broadly used therapeutic regimen against various cancers. However, the insufficient cellular uptake, deactivation by thiol-containing species and nonspecific distribution of cisplatin (CDDP) result in its low chemosensitivity as well as systemic side effects, which can largely constrain the employment of CDDP in clinical treatment. To circumvent these problems, in this study, polymeric nanoparticles were utilized to codeliver a water-soluble CDDP derivative, poly(γ,l-glutamic acid)-CDDP conjugate, and a naturally occurring compound derived from broccoli, sulforaphane, which can achieve efficient glutathione (GSH) depletion, to improve the accumulation of CDDP in cancer cells. Results show that compared with combinational treatment of CDDP and SFN, the nanoparticles were more effectively internalized and could significantly reduce GSH content in breast cancer cells, leading to a notable increase in DNA-bound Pt and DNA damage-induced apoptosis. Moreover, in an orthotopic breast cancer model, the nanoparticles achieved a significantly higher tumor accumulation and exhibited a more powerful antitumor activity. Finally, this nanoenhanced chemotherapy was further confirmed in a liver cancer model with high-expression of GSH. Taken together, this sulforaphane-based nanostrategy holds great promise to enhance the sensitivity and therapeutic efficacy of Pt-based chemotherapy.

Synthesis and Imaging of Biocompatible Graphdiyne Quantum Dots.

Graphdiyne has attracted much interest from researchers for their potential applications in energy storage, catalysis, and biomedical areas. As one of the derivatives of graphdiyne, graphdiyne quantum dots (GDQDs) may possess superior bioactivity due to active acetylene units. However, the biological application of biocompatible GDQDs have not been reported so far. Herein, GDQDs with uniform size and good crystallization were prepared via a classical solvothermal method. The GDQDs exhibit excitation- and pH-dependent fluorescence emission as well as superior photostability, demonstrating their potential for bioimaging. The GDQDs demonstrate efficient cellular uptake and cell imaging without induction of detectable cytotoxic effects in vitro. Systematical safety evaluation further confirmed good biocompatibility of the GDQDs in vivo. Our study preliminarily validates the application of the GDQDs in biomedicine and encourages more thorough studies for better realizing the potential of GDQDs.

Dopamine Delivery via pH-Sensitive Nanoparticles for Tumor Blood Vessel Normalization and an Improved Effect of Cancer Chemotherapeutic Drugs.

Tumor blood vessels have been reported to be abnormal in both structure and function compared with those in normal tissues, leading to a hostile microenvironment and inadequate antitumor drug delivery. Dopamine, a chemical messenger, is proven to inhibit angiogenesis and improve tumor vessel normalization. Here, a mesoporous silicon nanoparticle (MSN) is constructed that is responsive to the weakly acidic pH of the tumor extracellular matrix for steady delivery and tumor-localized release of dopamine. Then MSNs are functionalized with amine conjugated phenylboronicacid molecules, and dopamine is loaded by reacting with phenylboronic acid. In a weakly acidic environment, MSNs intelligently release dopamine due to the hydrolysis of boronic-ester bond between dopamine and phenylboronic acid, resulting in an evident inhibition of vascular endothelial cell migration and tubule formation. It is shown that loading of dopamine into the functional MSNs significantly prolong the circulatory half-life of this small molecule. After intravenous injection to tumor bearing mice, this nanoformulation induce tumor blood vessel normalization, thereby improving the antitumor chemotherapeutic efficacy of doxorubicin. This study demonstrates that the pH-responsive MSN offers great potential for delivery of dopamine in vivo and the normalization of tumor vessels by dopamine can provide an auxiliary treatment for cancer chemotherapeutic drugs.

An Extendable Star-Like Nanoplatform for Functional and Anatomical Imaging-Guided Photothermal Oncotherapy.

Combining informative imaging methodologies with effective treatments to destroy tumors is of great importance for oncotherapy. Versatile nanotheranostic agents that inherently possess both diagnostic imaging and therapeutic capabilities are highly desirable to meet these requirements. Here, a simple but powerful nanoplatform based on polydopamine-coated gold nanostar (GNS@PDA), which can be easily diversified to achieve various function extensions, is designed to realize functional and anatomical imaging-guided photothermal oncotherapy. This nanoplatform intrinsically enables computed tomography/photoacoustic/two-photon luminescence/infrared thermal tetramodal imaging and can further incorporate fibroblast activation protein (FAP, a protease highly expressed in most of tumors) activatable near-infrared fluorescence imaging and Fe3+-based magnetic resonance imaging for comprehensive diagnosis. Moreover, GNS@PDA exhibits excellent photothermal performance and efficient tumor accumulation. Under the precise guidance of multimodal imaging, GNS@PDA conducts homogeneous photothermal ablation of bulky solid tumors (∼200 mm3) in a xenograft mouse model. These results suggest great promise of this extendable nanoplatform for cancer theranostics.

Peptide Self-Assembly Nanoparticles Loaded with Panobinostat to Activate Latent Human Immunodeficiency Virus.

Highly active antiretroviral therapy (HAART) can turn human immunodeficiency virus-1 (HIV-1) infection into a controllable chronic disease, but because of the presence of an HIV reservoir, it cannot completely eliminate the virus in HIV-infected patients. The activation of latent reservoirs is the key to the successful treatment of acquired immune deficiency syndrome (AIDS). As a class of latency-reversing agents (LRAs), histone deacetylase inhibitors (HDACis), such as panobinostat, have been the most widely investigated, but most of them have resulted in only a modest and transient activation of HIV latency. To improve the potency of latency activation, an injectable peptide self-assembly nanoparticle loaded with panobinostat (PNP-P) was designed with the ability to efficiently penetrate the cell to achieve better drug delivery and activation of latent HIV. The results confirmed that these nanoparticles could activate latently infected cells in vitro and in vivo and activate peripheral blood mononuclear cells (PBMCs) from latently infected patients ex vivo. Increased cellular drug uptake made the PNP-P more effective than panobinostat alone. Therefore, this strategy demonstrates that nanotechnology can help improve the activation of latent HIV, and this study lays a foundation for further development of LRA delivery systems for use against an HIV reservoir.

Biomimetic Metal-Organic Framework Nanoparticles for Cooperative Combination of Antiangiogenesis and Photodynamic Therapy for Enhanced Efficacy.

Photodynamic therapy (PDT) is a promising anticancer treatment and is clinically approved for different types of tumors. However, current PDT suffers several obstacles, including its neutralization by excess glutathione (GSH) in the tumor tissue and its strongly proangiogenic tumor response. In this work, a biomimic, multifunctional nanoparticle-based PDT agent, combining a tumor-targeted photosensitizer with GSH scavenging and antiangiogenesis therapy, is developed. A porphyrinic Zr-metal-organic framework nanoparticle is used simultaneously as the photosensitizer and the delivery vehicle of vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor apatinib. The core nanoparticles are wrapped in MnO2 to consume the intratumoral GSH and then decorated with a tumor cell membrane camouflage. After intravenous administration, the nanoparticles selectively accumulate in tumor through homotypic targeting mediated by the biomimic decoration, and the combination of enhanced PDT and antiangiogenic drug significantly improves their tumor inhibition efficiency. This study provides an integrated solution for mechanism-based enhancement of PDT and demonstrates the encouraging potential for multifunctional nanosystem applicable for tumor therapy.

Reversing tumor stemness via orally targeted nanoparticles achieves efficient colon cancer treatment.

The acquisition of stemness in colorectal cancer (CRC) attributed to the recurrence and metastasis in CRC treatment. Therefore, targeting the stemness of CRC forms a basis for the development of novel therapeutic approaches. However, the pain and systemic side effect from long-term of venipuncture injection remain great challenges to neoplastic treatment. Here, we introduce an oral drug delivery system for sustained release of BMI-1 inhibitor (PTC209) that reverses the stemness of CRC to overcome these obstacles. In this system, nanoparticles modified with hyaluronic acid (HA) showed high-affinity to CD44/CD168 overexpressed-CRC cells, and efficiently targeted to tumor site in a metastatic orthotropic colon cancer mouse model by oral administration. Significantly, the observed tumor growth inhibition is accompanied by decreased expression of stemness markers in the tumor tissues. Furthermore, HA-NPs-PTC209 also significantly prevented metastasis to the gastrointestinal system, while failing to exhibit acute side effects. In summary, we have developed an orally active, easily synthesized nanomedicine that shows promise for the treatment of colon cancer.

Cooperatively Responsive Peptide Nanotherapeutic that Regulates Angiopoietin Receptor Tie2 Activity in Tumor Microenvironment To Prevent Breast Tumor Relapse after Chemotherapy.

Expressed in macrophages and endothelial cells, the receptor for angiopoietin, tyrosine kinase with immunoglobulin and epidermal growth factor homology-2 (Tie2), is required for the reconstruction of blood vessels in tumor recurrence after chemotherapy. Thus, small therapeutic peptides that target and block Tie2 activity are promising as a therapeutic for the prevention of tumor relapse after chemotherapy. However, such small peptides often have low bioavailability, undergo rapid enzymatic degradation, and exhibit a short circulation half-life, making them ineffective in cancer therapy. Herein, we designed a dual-responsive amphiphilic peptide (mPEG1000-K(DEAP)-AAN-NLLMAAS) to modify the small peptide T4 (NLLMAAS) as a Tie2 inhibitor, endowing it with the ability to endure in circulation and specifically target tumor tissue. The ultimate nanoformulation (P-T4) releases T4 in response to the combination of the acidic tumor microenvironment and the presence of legumain, which is commonly overexpressed in tumor tissue. Compared with free T4, P-T4 decreases vessel density significantly (free T4: 2.44 ± 1.20%, P-T4: 0.90 ± 0.75%), delays tumor regrowth after chemotherapy (free T4: 43.2 ± 11.8%, P-T4: 63.6 ± 13.9%), and reduces distant metastasis formation (free T4: 4.50 ± 2.40%, P-T4: 0.67 ± 0.32%). These effects of P-T4 are produced by the local blockage of Tie2 signals in Tie2-positive macrophages and endothelial cells. In addition to describing a potential strategy to enhance circulation half-life and the accumulation of an active peptide at tumor sites, our approach exemplifies the successful targeting of multiple cell types that overexpress a key molecule in conditions associated with tumors.

Injectable Hexapeptide Hydrogel for Localized Chemotherapy Prevents Breast Cancer Recurrence.

Although postsurgical chemotherapy is frequently used for the treatment of breast cancer, tumor recurrence is still a frequent event. Enhancing the efficacy of chemotherapy via localized drug delivery may help to prevent breast cancer recurrence. To achieve this goal, we designed a hydrogel nanocarrier that could be injected at the tumor site by coassembly of tailor-made hexapeptide and doxorubicin. Evidently, on the basis of our findings, the sustained release of drug from the hydrogel led to a reduction in cancer recurrence, including the suppression of primary regrowth and distant metastasis. This localized chemotherapy strategy did not show any obvious side effects in vivo and represents a promising adjuvant therapeutic strategy for breast cancer recurrence.