Folic acid-conjugated bovine serum albumin-coated selenium-ZIF-8 core/shell nanoparticles for dual target-specific drug delivery in breast cancer.

Methotrexate (MTX), a frequently used chemotherapeutic agent, has limited water solubility, leading to rapid clearance even in local injections. In the present study, we developed folic acid-conjugated BSA-stabilized selenium-ZIF-8 core/shell nanoparticles for targeted delivery of MTX to combat breast cancer. FT-IR, XRD, SEM, TEM, and elemental mapping analysis confirmed the successful formation of FA-BSA@MTX@Se@ZIF-8. The developed nano-DDS had a mean diameter, polydispersity index, and zeta potential of 254.8 nm, 0.17, and - 16.5 mV, respectively. The release behavior of MTX from the nanocarriers was pH-dependent, where the cumulative release percentage at pH 5.4 was higher than at pH 7.4. BSA significantly improved the blood compatibility of nanoparticles so that after modifying their surface with BSA, the percentage of hemolysis decreased from 12.67 to 5.12%. The loading of methotrexate in BSA@Se@ZIF-8 nanoparticles reduced its IC50 on 4T1 cells from 40.29 µg/mL to 16.54 µg/mL, and by conjugating folic acid on the surface, this value even decreased to 12.27 µg/mL. In vivo evaluation of the inhibitory effect in tumor-bearing mice showed that FA-BSA@MTX@Se@ZIF-8 caused a 2.8-fold reduction in tumor volume compared to the free MTX, which is due to the anticancer effect of selenium nanoparticles, the pH sensitivity of ZIF-8, and the presence of folic acid on the surface as a targeting agent. More importantly, histological studies and animal body weight monitoring confirmed that developed nano-DDS does not have significant organ toxicity. Taking together, the incorporation of chemotherapeutics in folic acid-conjugated BSA-stabilized selenium-ZIF-8 nanoparticles may hold a significant impact in the field of future tumor management.

A Bioinspired Photosensitizer Performs Tumor Thermoresistance Reversion to Optimize the Atraumatic Mild-Hyperthermia Photothermal Therapy for Breast Cancer.

Mild-hyperthermia photothermal therapy (mPTT) has therapeutic potential with minimized damage to normal tissues. However, the poorly vascularized tumor area severely hampers the penetration of photothermal agents (PTAs), resulting in their heterogeneous distribution and the subsequent heterogeneous local temperature during mPTT. The presence of regions below the therapeutic 42 °C threshold can lead to incomplete tumor ablation and potential recurrence. Additionally, tumor anti-apoptosis and cytoprotection pathways, particularly activated thermoresistance, can nullify mild hyperthermia-induced tumor damage. Therefore, a bioinspired photosensitizer decorated with leucine to form biomimetic nanoclusters (CP-PLeu nanoparticles (NPs)) aimed at achieving rapid and homogeneous accumulation in tumors, is introduced. Moreover, CP-PLeu exhibits photodynamic effects that reverse tumor thermoresistance and physiological repair mechanisms, thereby inhibiting tumor resistance to hyperthermia. With the addition of NIR-II laser irradiation, CP-PLeu optimizes the therapeutic efficacy of mPTT and contributes to a minimally invasive therapeutic process for breast cancer. This therapeutic strategy, utilizing a biomimetic photosensitizer for homogeneous distribution of therapeutic temperature and photoactivated reversal of tumor thermoresistance, successfully achieves efficient breast tumor inhibition through an atraumatic mPTT process.

A polylysine/hyaluronan-based core-shell nanoparticle triggers drug delivery by ATP/hyaluronidase dual stimuli for inducing apoptosis of breast cancer cells.

The limitations of self-assembled polymeric nanoparticles for cancer therapy, including instability in the bloodstream, non-specific targeting of cancer cells, and unregulated intracellular drug delivery, were effectively addressed by the development of core-shell SNX@PLL-FPBA/mHA NPs. The core was SNX@PLL-FPBA NPs prepared from polylysine conjugated 3-fluoro-4-carboxyphenylboronic acid (PLL-FPBA) self-assembly and SNX encapsulation, while the shell was methacrylate-modified hyaluronic acid (mHA) adhering to the core by electrostatic interactions and subsequently stabilized by photo-crosslinking, without the use of any organic solvent. SNX@PLL-FPBA/mHA NPs exhibited good stability in varying ionic strengths (0-0.30 M NaCl), pH levels (6.8 and 7.4), and plasma environments mimicking the blood, ensuring their efficacy in systemic circulation. The drug delivery from the nanoparticles was highly sensitive to ATP/Hyals stimuli (82 % within 48 h), closely mimicking the intracellular environment of breast cancer cells. The nanoparticles demonstrated good hemocompatibility and non-toxicity towards human skin fibroblasts. Efficient internalization of SNX@PLL-FPBA/mHA NPs by MCF-7 and MDA-MB-231 breast cancer cells was observed by CLSM and flow cytometry. The intracellular ATP/Hyals stimuli triggered the rapid drug delivery and induced cellular apoptosis. Thus, SNX@PLL-FPBA/mHA NPs were a promising drug nanocarrier for breast cancer therapy, offering improved stability, targeted delivery, and controlled drug release to enhance treatment outcomes.

[FeIIICl(TMPPH2)][FeIIICl4]2: A Stand-Alone Molecular Nanomedicine That Induces High Cytotoxicity by Ferroptosis.

Developing clinically meaningful nanomedicines for cancer therapy requires the drugs to be effective, safe, simple, cheap, and easy to store. In the present work, we report that a simple cationic Fe(III)-rich salt of [FeIIICl(TMPPH2)][FeIIICl4]2 (Fe-TMPP) exhibits a superior anticancer performance on a broad spectrum of cancer cell lines, including breast, colorectal cancer, liver, pancreatic, prostate, and gastric cancers, with half maximal inhibitory concentration (IC50) values in the range of 0.098-3.97 µM (0.066-2.68 µg mL-1), comparable to the best-reported medicines. Fe-TMPP can form stand-alone nanoparticles in water without the need for extra surface modification or organic-solvent-assisted antisolvent precipitation. Critically, Fe-TMPP is TME-responsive (TME = tumor microenvironment), and can only elicit its function in the TME with overexpressed H2O2, converting H2O2 to the cytotoxic •OH to oxidize the phospholipid of the cancer cell membrane, causing ferroptosis, a programmed cell death process of cancer cells.

Bioactive Nanotherapeutic Ultrasound Contrast Agent for Concurrent Breast Cancer Ultrasound Imaging and Treatment.

Contrast-enhanced ultrasound (CEUS) plays a crucial role in cancer diagnosis. The use of ultrasound contrast agents (UCAs) is inevitable in CEUS. However, current applications of UCAs primarily focus on enhancing imaging quality of ultrasound contrast rather than serving as integrated platforms for both diagnosis and treatment in clinical settings. In this study, a novel UCA, termed NPs-DPPA(C3F8), is innovatively prepared using a combination of nanoprecipitation and ultrasound vibration methods. The DPPA lipid possesses inherent antiangiogenic and antitumor activities, and when combined with C3F8, it functions as a theranostic agent. Notably, the preparation of NPs-DPPA(C3F8) is straightforward, requiring only one hour from raw materials to the final product due to the use of a single material, DPPA. NPs-DPPA(C3F8) exhibits inherent antiangiogenic and biotherapeutic activities, effectively inhibiting triple-negative breast cancer (TNBC) angiogenesis and reducing VEGFA expression both in vitro and in vivo. Clinically, NPs-DPPA(C3F8) enables simultaneous real-time imaging, tumor assessment, and antitumor activity. Additionally, through ultrasound cavitation, NPs-DPPA(C3F8) can overcome the dense vascular walls to increase accumulation at the tumor site and facilitate internalization by tumor cells. The successful preparation of NPs-DPPA(C3F8) offers a novel approach for integrating clinical diagnosis and treatment of TNBC.

Advances in inorganic nanoparticles-based drug delivery in targeted breast cancer theranostics.

Theranostic nanoparticles (NPs) have the potential to dramatically improve cancer management by providing personalized medicine. Inorganic NPs have attracted widespread interest from academic and industrial communities because of their unique physicochemical properties (including magnetic, thermal, and catalytic performance) and excellent functions with functional surface modifications or component dopants (e.g., imaging and controlled release of drugs). To date, only a restricted number of inorganic NPs are deciphered into clinical practice. This review highlights the recent advances of inorganic NPs in breast cancer therapy. We believe that this review can provides various approaches for investigating and developing inorganic NPs as promising compounds in the future prospects of applications in breast cancer treatment and material science.

Novel pH-responsive alginate-stabilized curcumin-selenium-ZIF-8 nanocomposites for synergistic breast cancer therapy.

In this study, a novel selenium@zeolitic imidazolate framework core/shell nanocomposite stabilised with alginate was used to improve the anti-tumour activity of curcumin. The developed alginate-stabilised curcumin-loaded selenium@zeolitic imidazolate framework (Alg@Cur@Se@ZIF-8) had a mean diameter of 159.6 nm and polydispersity index < 0.25. The release of curcumin from the nanocarrier at pH 5.4 was 2.69 folds as high as at pH 7.4. The bare nanoparticles showed haemolytic activity of about 12.16% at a concentration of 500 µg/mL while covering their surface with alginate reduced this value to 5.2%. By investigating cell viability, it was found that Alg@Cur@Se@ZIF-8 caused more cell death than pure curcumin. Additionally, in vivo studies showed that Alg@Cur@Se@ZIF-8 dramatically reduced tumour growth compared to free curcumin in 4T1 tumour-bearing mice. More importantly, the histological study confirmed that the developed drug delivery system successfully inhibited lung and liver metastasis while causing negligible toxicity in vital organs. Overall, due to the excellent inhibitory activity on cancerous cell lines and tumour-bearing animals, Alg@Cur@Se@ZIF-8 can be considered promising for breast cancer therapy.

Novel polyurethane-based ionene nanoparticles electrostatically stabilized with hyaluronic acid for effective gene therapy.

Gene therapy is considered to be a valuable strategy for effective cancer treatment. However, the development of effective delivery systems that can specifically deliver gene materials, such as siRNA to tumor tissues plays a critical role in cancer therapy. In the present study, we have developed a novel complex that is based on an electrostatic interaction between cationic polyurethane ionene (CPUI) nanoparticles and an anti-signal transducer and activator of transcription 3 (STAT3) siRNA. For active targeting, hyaluronic acid (HA) was used to coat the complexes, which significantly reduced the cytotoxicity of the blank nanocarriers while demonstrating high transport efficiency of the siRNA via the CD44-mediated endocytosis pathway in MCF-7 breast cancer cells. The targeted nanocarriers (HA/CPUI/siRNA) showed significantly higher cellular internalization in flow cytometry and confocal microscopy compared with the non-targeted system (CPUI/siRNA). In addition, the incorporation of HA on the surface of the complexes resulted in significantly greater suppression of the STAT3 gene compared to the corresponding non-targeted formulation. Whole-body fluorescence images showed more significant tumor accumulation of the targeted nanocarriers in 4T1 breast tumor-bearing mice. Therefore, HA/CPUI/siRNA nanocarriers are an interesting option for the siRNA-targeted treatment of breast cancer cells.

Cannabidiol Combination Enhances Photodynamic Therapy Effects on MCF-7 Breast Cancer Cells.

Cannabis sativa is a well-known plant for its psychoactive effects; however, its many derivatives, such as Cannabidiol (CBD), contain several therapeutic applications. Tetrahydrocannabinol (THC) is the main cannabis derivative responsible for psychoactive properties, while CBD is non-psychotropic. For this reason, CBD has been more exploited in the last decade. CBD has been connected to multiple anticancer properties, and when combined with photodynamic therapy (PDT), it is possible to eradicate tumors more effectively. In this study, CBD was utilized to treat MCF-7 breast cancer cells, followed by in vitro PDT combination therapy. Conventional breast cancer treatment modalities such as chemotherapy, radiotherapy, etc. have been reported for inducing a number of undesirable side effects, recurrence of the disease, and low quality of life. In this study, cells were exposed to varying concentrations of CBD (i.e., 1.25, 2.5, 5, 10, and 20 µg/mL) and incubated 12 and 24 h after treatment. The optimal doses were then used in combination therapy. Morphology and biochemical assays, including lactate dehydrogenase (LDH) for membrane integrity, adenosine triphosphate (ATP) for viability, and trypan blue exclusion assay for viability, were used to examine cellular responses after treatments. The optimal concentration was then utilized in Hypericin-Gold nanoparticles mediated PDT combination. The results revealed that, in a dose-dependent manner, conventional morphological characteristics of cell death, such as vacuolization, blebbing, and floating were observed in treated cells. The biochemical responses demonstrated an increase in LDH, a decrease in ATP, and a reduction in viability. This study demonstrated that CBD induces cell death in MCF-7 breast cancer cells cultured in vitro. The immunofluorescence results of combination therapy indicated that cell death occurred via apoptosis. In conclusion, this study proposes that the CBD and PDT combination therapy is effective in killing MCF-7 breast cancer cells in vitro by induction of apoptosis.

Glutamate affects self-assembly, protein corona, and anti-4 T1 tumor effects of melittin/vitamin E-succinic acid-(glutamate)n nanoparticles.

Melittin (M) has attracted increasing attention for its significant antitumor effects and various immunomodulatory effects. However, various obstacles such as the short plasma half-life and adverse reactions restrict its application. This study aimed to systematically investigate the self-assembly mechanism, components of the protein corona, targeting behavior, and anti-4 T1 tumor effect of vitamin E-succinic acid-(glutamate)n /melittin nanoparticles with varying amounts of glutamic acid. Here, we present a new vitamin E-succinic acid-(glutamate)5 (E5), vitamin E-succinic acid-(glutamate)10 (E10) or vitamin E-succinic acid-(glutamate)15 (E15), and their co-assembly system with positively charged melittin in water. The molecular dynamics simulations demonstrated that the electrostatic energy and van der Waals force in the system decreased significantly with the increase in the amount of glutamic acid. The melittin and E15 system exhibited the optimal stability for nanoparticle self-assembly. When nanoparticles derived from different self-assembly systems were co-incubated with plasma from patients with breast cancer, the protein corona showed heterogeneity. In vivo imaging demonstrated that an increase in the number of glutamic acid residues enhanced circulation duration and tumor-targeting effects. Both in vitro and in vivo antitumor evaluation indicated a significant increase in the antitumor effect with the addition of glutamic acid. According to our research findings, the number of glutamic acid residues plays a crucial role in the targeted delivery of melittin for immunomodulation and inhibition of 4 T1 breast cancer. Due to the self-assembly capabilities of vitamin E-succinic acid-(glutamate)n in water, these nanoparticles carry significant potential for delivering cationic peptides such as melittin.

Discovery of X10g as a selective PROTAC degrader of Hsp90α protein for treating breast cancer.

Heat shock protein 90 (Hsp90), a highly conserved and widely expressed molecular chaperone, is mainly responsible for maintaining the correct folding of client proteins and is closely related to the stability and activation of tumour-related proteins. Hsp90α, the major isoform of Hsp90, can promote tumour cell migration and metastasis, and is abundantly secreted in highly invasive tumours. To date, most pan-Hsp90 inhibitors have been limited in their applications due to high toxicity. Herein, we described the candidate compound X10g based on a proteolysis-targeting chimaera (PROTAC) strategy that potently and selectively degraded Hsp90α. The results showed that X10g inhibited tumours better with lower toxicity in vivo. These findings demonstrate that synthesized selective Hsp90α degrader X10g provides a new strategy for breast cancer therapy.

Coordination-driven FBXW7 DNAzyme-Fe nanoassembly enables a binary switch of breast cancer cell cycle checkpoint responses for enhanced ferroptosis-radiotherapy.

Radiotherapy is a mainstream modality for breast cancer treatment that employs ionizing radiation (IR) to damage tumor cell DNA and elevate ROS stress, which demonstrates multiple clinically-favorable advantages including localized treatment and low invasiveness. However, breast cancer cells may activate the p53-mediated cell cycle regulation in response to radiotherapy to repair IR-induced cellular damage and facilitate post-treatment survival. F-Box and WD Repeat Domain Containing 7 (FBXW7) is a promoter of p53 degradation and critical nexus of cell proliferation and survival events. Herein, we engineered a cooperative radio-ferroptosis-stimulatory nanomedicine through coordination-driven self-assembly between ferroptosis-inducing Fe2+ ions and FBXW7-inhibiting DNAzymes and further modification of tumor-targeting dopamine-modified hyaluronic acid (HA). The nanoassembly could be selectively internalized by breast cancer cells and disintegrated in lysosomes to release the therapeutic payload. DNAzyme readily abolishes FBXW7 expression and stabilizes phosphorylated p53 to cause irreversible G2 phase arrest for amplifying post-IR tumor cell apoptosis. Meanwhile, the p53 stabilization also inhibits the SLC7A11-cystine-GSH axis, which combines with the IR-upregulated ROS levels to amplify Fe2+-mediated ferroptotic damage. The DNAzyme-Fe-HA nanoassembly could thus systematically boost the tumor cell damaging effects of IR, presenting a simple and effective approach to augment the response of breast cancer to radiotherapy. STATEMENT OF SIGNIFICANCE: To overcome the intrinsic radioresistance in breast cancer, we prepared co-assembly of Fe2+ and FBXW7-targeted DNAzymes and modified surface with dopamine conjugated hyaluronic acid (HA), which enabled tumor-specific FBXW7-targeted gene therapy and ferroptosis therapy in IR-treated breast cancers. The nanoassembly could be activated in acidic condition to release the therapeutic contents. Specifically, the DNAzymes could selectively degrade FBXW7 mRNA in breast cancer cells to simultaneously induce accumulation of p53 and retardation of NHEJ repair, eventually inducing irreversible cell cycle arrest to promote apoptosis. The p53 stabilization would also inhibit the SLC7A11/GSH/GPX4 axis to enhance Fe2+ mediated ferroptosis. These merits could act in a cooperative manner to induce pronounced tumor inhibitory effect, offering new approaches for tumor radiosensitization in the clinics.

Taxane-Induced Neuropathy and Its Ocular Effects-A Longitudinal Follow-up Study in Breast Cancer Patients.

A common severe neurotoxic side effect of breast cancer (BC) therapy is chemotherapy-induced peripheral neuropathy (CIPN) and intervention is highly needed for the detection, prevention, and treatment of CIPN at an early stage. As the eye is susceptible to neurotoxic stimuli, the present study aims to determine whether CIPN signs in paclitaxel-treated BC patients correlate with ocular changes by applying advanced non-invasive biophotonic in vivo imaging. Patients (n = 14, 10 controls) underwent monitoring sessions after diagnosis, during, and after therapy (T0-T3). Monitoring sessions included general anamnesis, assessment of their quality of life, neurological scores, ophthalmological status, macular optical coherence tomography (OCT), and imaging of their subbasal nerve plexus (SNP) by large-area confocal laser-scanning microscopy (CLSM). At T0, no significant differences were detected between patients and controls. During treatment, patients' scores significantly changed while the greatest differences were found between T0 and T3. None of the patients developed severe CIPN but retinal thickenings could be detected. CLSM revealed large SNP mosaics with identical areas while corneal nerves remained stable. The study represents the first longitudinal study combining oncological examinations with advanced biophotonic imaging techniques, demonstrating a powerful tool for the objective assessment of the severity of neurotoxic events with ocular structures acting as potential biomarkers.

Outcomes of a Multidisciplinary Team in the Management of Patients with Early-Stage Breast Cancer Undergoing Neoadjuvant Chemotherapy at a Community Cancer Center.

Background: The utilization of neoadjuvant chemotherapy (NAC) remains highly variable in clinical practice. The implementation of NAC requires coordination of handoffs between a multidisciplinary team (MDT). This study aims to assess the outcomes of an MDT in the management of early-stage breast cancer patients undergoing neoadjuvant chemotherapy at a community cancer center. Methods: We conducted a retrospective case series on patients receiving NAC for early-stage operable or locally advanced breast cancer coordinated by an MDT. Outcomes of interest included the rate of downstaging of cancer in the breast and axilla, time from biopsy to NAC, time from completion of NAC to surgery, and time from surgery to radiation therapy (RT). Results: Ninety-four patients underwent NAC; 84% were White and mean age was 56.5 yrs. Of them, 87 (92.5%) had clinical stage II or III cancer, and 43 (45.8%) had positive lymph nodes. Thirty-nine patients (42.9%) were triple negative, 28 (30.8%) were human epidermal growth factor receptor (HER-2)+, and 24 (26.2%) were estrogen receptor (ER) +HER-2-. Of 91 patients, 23 (25.3%) achieved pCR; 84 patients (91.4%) had downstaging of the breast tumor, and 30 (33%) had axillary downstaging. The median time from diagnosis to NAC was 37.5 days, the time from completion of NAC to surgery was 29 days, and the time from surgery to RT was 49.5 days. Conclusions: Our MDT provided timely, coordinated, and consistent care for patients with early-stage breast cancer undergoing NAC as evidenced by time to treatment outcomes consistent with recommended national trends.

Cell- and subcellular organelle-targeting nanoparticle-mediated breast cancer therapy.

Breast cancer (BC) is the most prevalent malignant tumor, surpassing lung cancer as the most frequent malignancy in women. Drug resistance, metastasis, and immune escape are the major factors affecting patient survival and represent a huge challenge in BC treatment in clinic. The cell- and subcellular organelle-targeting nanoparticles-mediated targeted BC therapy may be an effective modality for immune evasion, metastasis, and drug resistance. Nanocarriers, efficiently delivering small molecules and macromolecules, are used to target subcellular apparatuses with excellent targeting, controlled delivery, and fewer side effects. This study summarizes and critically analyzes the latest organic nanoparticle-mediated subcellular targeted therapeutic based on chemotherapy, gene therapy, immunotherapy, and combination therapy in detail, and discusses the challenges and opportunities of nanoparticle therapy.

Sexual dysfunctions in breast cancer patients: evidence in context.

INTRODUCTION: In breast cancer patients, endocrine therapy may exert a negative impact on sexual functioning in both genders, with potentially relevant consequences concerning quality of life and treatment adherence. The availability of effective interventions to maintain and/or restore sexual health in breast cancer patients is a key issue to a research agenda. OBJECTIVES: To summarize and critically discuss the most updated and qualitatively relevant literature on the therapeutic approach to sexual impairment in breast cancer patients, with a focus on patients treated with endocrine therapy. METHODS: We searched PubMed from its inception to February 2022 for observational and intervention trials including participants with sexual dysfunctions. We were particularly interested in studies of breast cancer patients with sexual dysfunctions while undergoing endocrine therapy. We developed a search strategy with the aim of maximizing the number of articles considered for screening and potential inclusion. RESULTS: Forty-five studies were selected: 3 observational and 42 intervention studies. Thirty-five studies were exclusively focused on female breast cancer populations. We could not identify studies exclusively focused on or also including male breast cancer patients. Overall, in female patients, the available armamentarium encompasses vaginal lubricants, moisturizers, estrogens, dehydroepiandrosterone, CO2 laser, ospemifene, and counseling. None of these interventions has been demonstrated to completely solve sexual dysfunctions when singularly considered. More favorable outcomes have come from the combination of different therapies. CONCLUSION: In female breast cancer, future research is oriented toward the gain of evidence on combined therapies and long-term data on safety issues on the most promising interventions. The lack of evidence on sexual disturbances in male breast cancer patients remains a major concern.

Folic-acid adorned alginate-polydopamine modified paclitaxel/Zn-CuO nanocomplex for pH triggered drug release and synergistic antitumor efficacy.

Targeted chemotherapy is a prominent cancer treatment research trend that intends to boost the efficacy of drug delivery to cancer cells. The present work aimed to design, a folate-decorated biologically inspired alginate-polydopamine capped zinc doped copper oxide nanoparticles (Zn-CuO) loaded with paclitaxel (Zn-CuO@PTX/AlgPDA-FA) as a simple, efficient, and versatile nanoplatform. Interestingly, Zn species doped in CuO frameworks significantly improved paclitaxel (PTX) molecule loading efficiency without requiring any additional functionalization and fostered the increased antitumor efficacy by precisely delivering them in tumor's acidic microenvironment by obliterating the formed coordination connections between the host as well as guest species. According to DLS, average size of nanocomplex was 196 ± 5.01 nm with È¥-potential -31.4 ± 1.54 mV. PTX encapsulation and loading efficiencies were 75.2 ± 1.54 % and 18.54 ± 2.31 %, respectively. Furthermore, nanocomplex demonstrates high stability and biocompatibility in vitro. Under an acidic environment (pH 5.0), there was greater PTX release compared to normal physiological conditions. Moreover, Zn-CuO@PTX/AlgPDA-FA NPs showed remarkable internalization efficiency in MCF-7 cells and demonstrated strong cytotoxicity with IC50 (150 ± 2.58 µg/mL) along with improved ROS generation and changed mitochondrial membrane potential level. Therefore, our approach could suggest excellent potential for tumor targeting in cancer therapy with reduced off-target toxicity, and desirable therapeutic effects.

Smart Chondroitin Sulfate Micelles for Effective Targeted Delivery of Doxorubicin Against Breast Cancer Metastasis.

Introduction: Metastasis is a major challenge in breast cancer therapy. The successful chemotherapy of breast cancer largely depends on the ability to block the metastatic process. Herein, we designed a dual-targeting and stimuli-responsive drug delivery system for targeted drug delivery against breast cancer metastasis. Methods: AS1411 aptamer-modified chondroitin sulfate A-ss-deoxycholic acid (ACSSD) was synthesized, and the unmodified CSSD was used as the control. Chemotherapeutic drug doxorubicin (DOX)-containing ACSSD (D-ACSSD) micelles were prepared by a dialysis method. The ACSSD conjugate was confirmed by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). In vitro cellular uptake and cytotoxicity of D-ACSSD micelles were studied by confocal laser scanning microscopy (CLSM) and MTT assay in breast tumor cells. The inhibition capability of D-ACSSD micelles in cell migration and invasion was carried out in 4T1 cells. In vivo antitumor activity of DOX-containing micelles was investigated in metastatic 4T1-bearing Balb/c mice. Results: D-ACSSD and DOX-loaded CSSD (D-CSSD) micelles exhibited high drug encapsulation content and reduction-responsive characteristics. D-ACSSD micelles were spherical in shape. Compared with D-CSSD, D-ACSSD showed higher cellular uptake and more potent killing activity in 4T1 and MDA-MB-231 cells. Additionally, D-ACSSD exhibited stronger inhibitory effects on the invasion and migration of highly metastatic 4T1 cells than unmodified D-CSSD. Among the DOX-containing formulations, D-ACSSD micelles presented the most effective inhibition of tumor growth and lung metastasis in orthotopic 4T1-bearing mice in vivo. It also revealed that ACSSD micelles did not exhibit obvious systemic toxicity. Conclusion: The smart D-ACSSD micelles could be a promising delivery system for the therapy of metastatic breast cancer.

Single Atom-Doped Nanosonosensitizers for Mutually Optimized Sono/Chemo-Nanodynamic Therapy of Triple Negative Breast Cancer.

Sonodynamic therapy (SDT) represents a promising therapeutic modality for treating breast cancer, which relies on the generation of abundant reactive oxygen species (ROS) to induce oxidative stress damage. However, mutant breast cancers, especially triple-negative breast cancer (TNBC), have evolved to acquire specific antioxidant defense functions, significantly limiting the killing efficiency of SDT. Herein, the authors have engineered a distinct single copper atom-doped titanium dioxide (Cu/TiO2 ) nanosonosensitizer with highly catalytic and sonosensitive activities for synergistic chemodynamic and sonodynamic treatment of TNBC. The single-atom Cu is anchored on the most stable Ti vacancies of hollow TiO2 sonosensitizers, which not only substantially improved the catalytic activity of Cu-mediated Fenton-like reaction, but also considerably augmented the sonodynamic efficiency of TiO2 by facilitating the separation of electrons (e- ) and holes (h+ ). Both the in vitro and in vivo studies demonstrate that the engineered single atom-doped nanosonosensitizers effectively achieved the significantly inhibitory effect of TNBC, providing a therapeutic paradigm for non-invasive and safe tumor elimination through the mutual process of sono/chemo-nanodynamic therapy based on multifunctional single-atom nanosonosensitizers.

De-Escalating Breast Cancer Therapy.

The potential value of de-escalation in breast cancer therapy cannot be overstated. From reducing complications and morbidity of surgical therapy to the avoidance of chemotherapy in certain populations, the benefits of eliminating low-value therapies are significant. Further, those interventions that have minimal to no benefit may also further low-risk care cascades resulting in additional treatments or interventions without associated value, with increased financial toxicity, and resulting excess health care expenditures.