Doxorubicin Nanoparticles Research Articles

Potentiated Calcium Carbonate with Enhanced Calcium Overload Induction and Acid Neutralization Capabilities to Boost Chemoimmunotherapy against Liver Cancer.

Unfavorable phenotypes characterized by low immunogenicity and acidity within the tumor microenvironment (TME) contribute to immunosuppression and therapeutic resistance. Herein, we rationally synthesized a multifunctional nanoregulator by encapsulating DOX and erianin into calcium carbonate (CaCO3)-based nanoparticles using a modified double emulsion method. The DOX and erianin-loaded CaCO3-based nanoparticles, termed DECaNPs, could effectively induce the calcium overload by triggering calcium influx and absorbing CaCO3 nanoparticles. Additionally, DECaNPs also neutralize the acidic TME by interacting with extracellular protons and limiting lactic acid production, a result of metabolic remodeling in cancer cells. As a result, DECaNPs elicit cellular oxidative stress damage, which mediates the activation of ferroptosis/apoptosis hybrid pathways, and profound immunogenic cell death. Treatment with DECaNPs could inhibit the growth of tumors by promoting oxidative stress, acid neutralization, metabolic remodeling, and protective antitumor immunity in vivo. In addition, DECaNPs could synergistically amplify the antitumor effects of αPD-L1 in a bilateral tumor model by eliciting systemic immune responses. In all, our work presents the preparation of CaCO3-based nanoregulators designed to reverse the unfavorable TME and enhance αPD-L1 immunotherapy through multiple mechanisms.

Formulation and Evaluation of Lungs-Specific Doxorubicin-Loaded Chitosan-PLGA-Alginate Polymeric Nanoparticles

Background: An antibiotic called doxorubicin is produced by the Streptomyces peuce-tius bacterium, which is a member of the anthracycline drug class and is used in chemotherapy. Usually, doxorubicin is employed to cure solid tumors in children and adult patients. The physical and biological stability of the medicine can be increased by encasing it in nanoparticles, which increases the active pharmaceutical ingredient's bioavailability. Objective: This study aimed to create lungs targeting doxorubicin-loaded biodegradable polymer-ic nanoparticulate system by utilizing an appropriate method and conducting its evaluation. Methods: The polymeric nanoparticles using biodegradable polymers were prepared by the emul-sion polymerization method. Franz- diffusion cells were utilized to conduct in-vitro drug diffu-sion investigations. Results: Based on the outcomes of the experiments carried out for the research, polymeric nano-particles of doxorubicin were prepared utilizing different concentrations of chitosan, Sodium al-ginate, and PLGA. The visual appearance of doxorubicin polymeric nanoparticles shows homo-geneous dispersion with no phase separation form. The percentage yield, % entrapment efficien-cy, and drug content obtained for the final formulation were 93.43 ± 1.776, 87.31 ± 1.075, and 91.98 ± 0.493, respectively. A size dimension of 174.51 nm with a PDI of 0.242 and zeta poten-tial value of -36.1 mV of prepared nanoparticles demonstrate the stability of the formulation. The presentation of the PNPs of the optimized formulation having 310mg Tween 80 showed in vitro diffusion of 98.93% ± 0.296 % and an increased flux rate. Based on the determination coeffi-cients, the Higuchi model (K0 = 20.43 and R2= 0.982) was determined to have the best fit for the release data. Conclusion: Based on the trials conducted during the investigation, it was determined that the emulsion polymerization technique was best for the fabrication of the polymeric nanoparticles by utilizing different concentrations of chitosan, Sodium alginate, and PLGA. The formulation F6 containing 310mg Tween 80 suggested improved in vitro diffusion following the Higuchi model throughout all formulations. The findings suggest that a sustained process was responsible for the drug's release from the doxorubicin polymeric nanoparticles.

Precision Treatment of Colon Cancer Using Doxorubicin-Loaded Metal-Organic-Framework-Coated Magnetic Nanoparticles.

Due to the limited efficacy and evident side effects of traditional chemotherapy drugs attributed to their lack of specificity and selectivity, novel strategies are essential for improving cancer treatment outcomes. Here, we successfully engineered Fe3O4 magnetic nanoparticles coated with zeolitic imidazolate framework-8 (ZIF-8). The resulting nanocomposite (Fe3O4@ZIF-8) demonstrates efficient adsorption of a substantial amount of doxorubicin (DOX) due to the porous nature of ZIF-8. The drug-loaded nanoparticles, Fe3O4@ZIF-8/DOX, exhibit significant accumulation at the tumor site in SW620 colon-cancer-bearing mice when guided by an external magnetic field. Within the acidic microenvironment of the tumor, the ZIF-8 framework collapses, releasing DOX and effectively inducing tumor cell death, thereby inhibiting cancer progression while not causing undesired side effects, as confirmed by a variety of in vitro and in vivo characterizations. In comparison to free DOX, Fe3O4@ZIF-8/DOX nanoparticles show superior efficacy in colon cancer treatment. Our findings suggest that Fe3O4@ZIF-8 holds promise as a carrier for small-molecule drug adsorption and its ferromagnetic properties provide drug targeting capabilities, thereby enhancing therapeutic effects on tumors at the same drug dosage. With excellent biocompatibility, Fe3O4@ZIF-8 demonstrates potential as a drug carrier in targeted cancer chemotherapy. Our work suggests that a combination of magnetic targeting and acid-responsiveness holds great promise for advancing targeted cancer therapy in precision nanomedicine.

Synthesis and application of multifunctional magnetic mesoporous nanomaterials with redox reaction and NIR response in tumor treatment

In recent years, the novel minimally invasive combination therapy for tumors has garnered widespread attention due to its controllable therapeutic target, effective combination therapy outcome, and minimal toxic side effects. This study integrated inorganic nanospheres of ferric oxide (Fe3O4) with mesoporous silica nanoparticles (MSN), along with polymeric organic polymers—polyaniline (PANI) and hyaluronic acid (HA)—to create a multifunctional tumor treatment platform (Fe3O4@MSN@PANI@HA), aiming to enhance the efficacy of therapies that have monotherapy limitations. The Fe2+ within the Fe3O4@MSN@PANI@HA nanoparticles can react with the unique hydrogen peroxide present in the tumor microenvironment to generate hydroxyl radicals (·OH), which possess cytotoxic properties that can selectively eradicate tumor cells, thereby facilitating chemodynamic therapy (CDT). Moreover, Fe3O4@MSN@PANI@HA nanoparticles, when loaded with the chemotherapy drug doxorubicin hydrochloride (DOX), yield Fe3O4@MSN@PANI@HA-DOX nanoparticles. It has been demonstrated that these nanoparticles exhibit commendable drug-loading efficiency and controlled drug-release capabilities, contributing to the chemotherapy of tumors. The inclusion of PANI in the Fe3O4@MSN@PANI@HA nanoparticles endows them with an exceptional photothermal conversion capability. Upon exposure to an 808-nm near-infrared laser (NIR), the photothermal conversion efficiency of the composite nanomaterials reaches 42.76 %, thereby enabling photothermal therapy (PTT) through the thermal ablation of tumor cells. The HA component of the composite nanoparticles provides excellent biocompatibility and a sustained drug-release effect. Simultaneously, it could target tumor cells by recognizing specific receptors that are overexpressed on the cell surfaces, directing the transport of the composite nanoparticles to the tumor site, and selectively destroying tumor cells. This paper confirms the potent therapeutic impact of composite nanoparticles on tumors and offers a novel perspective for designing multifunctional composite nanomaterials.

A Manganese-Based Nanodriver Coordinates Tumor Prevention and Suppression through STING Activation in Glioblastoma.

Glioblastoma (GBM), the most prevalent and aggressive primary malignant brain tumor, exhibits profound immunosuppression and demonstrates a low response rate to current immunotherapy strategies. Manganese cations (Mn2+) directly activate the cGAS/STING pathway and induce the unique catalytic synthesis of 2'3'-cGAMP to facilitate type I IFN production, thereby enhancing innate immunity. Here, a telodendrimer and Mn2+-based nanodriver (PLHM) with a small size is developed, which effectively target lymph nodes through the blood circulation and exhibit tumor-preventive effects at low doses of Mn2+ (3.7mg kg-1). On the other hand, the PLHM nanodriver also exhibits apparent antitumor effects in GBM-bearing mice via inducing in vivo innate immune responses. The combination of PLHM with doxorubicin nanoparticles (PLHM-DOX NPs) results in superior inhibition of tumor growth in GBM-bearing mice due to the synergistic potentiation of STING pathway functionality by Mn2+ and the presence of cytoplasmic DNA. These findings demonstrate that PLHM-DOX NPs effectively stimulate innate immunity, promote dendritic cell maturation, and orchestrate cascaded infiltration of CD8 cytotoxic T lymphocytes within glioblastomas characterized by low immunogenicity. These nanodivers chelated with Mn2+ show promising potential for tumor prevention and antitumor effects on glioblastoma by activating the STING pathway.

An oral bioactive chitosan-decorated doxorubicin nanoparticles/bacteria bioconjugates enhance chemotherapy efficacy in an in-situ breast cancer model

Breast cancer is the second leading cause of cancer-related deaths among women worldwide. Despite significant advancements in chemotherapy, its effectiveness is often limited by poor drug distribution and systemic toxicity caused by the weak targeting ability of conventional therapeutic agents. The hypoxic tumor microenvironment (TME) also plays a vital role in treatment outcomes. Oral anticancer therapeutic agents have gained popularity and show promising results due to their ease of repeated administration. This study introduces autopilot biohybrids (Bif@BDC-NPs) for the effective delivery of doxorubicin (DOX) to the tumor site. This hybrid combines albumin-encapsulated DOX nanoparticles (BD-NPs) coated with chitosan (CS) for breast cancer chemotherapy, along with anaerobic Bifidobacterium infantis (B. infantis, Bif) serving as self-propelled motors. Due to Bif's specific anaerobic properties, Bif@BDC-NPs precisely anchor hypoxic regions of tumor tissue and significantly increase drug accumulation at the tumor site, thereby promoting tumor cell death. In an in-situ mouse breast cancer model, Bif@BDC-NPs achieved 94 % tumor inhibition, significantly prolonging the median survival of mice to 62 days, and reducing the toxic side effects of DOX. Therefore, the new bacteria-driven oral drug delivery system, Bif@BDC-NPs, overcomes multiple physiological barriers and holds great potential for the precise treatment of solid tumors.

Tumor-targeted and stimulus-responsive polymeric prodrug nanoparticles to enhance the anticancer therapeutic efficacy of doxorubicin

Polymeric prodrug nanoparticles have gained increasing attention in the field of anticancer drug delivery because of their dual functions as a drug carrier and a therapeutic agent. Doxorubicin (DOX) is a highly effective chemotherapeutic agent for various cancers but causes cardiotoxicity. In this work, we developed polymeric prodrug (pHU) nanoparticles that serve as both a drug carrier of DOX and a therapeutic agent. The composition of pHU includes antiangiogenic hydroxybenzyl alcohol (HBA) and ursodeoxycholic acid (UDCA), covalently incorporated through hydrogen peroxide (H2O2)-responsive peroxalate. To enhance cancer cell specificity, pHU nanoparticles were surface decorated with taurodeoxycholic acid (TUDCA) to facilitate p-selectin-mediated cancer targeting. TUDCA-coated and DOX-loaded pHU nanoparticles (t-pHUDs) exhibited controlled release of DOX triggered by H2O2, characteristic of the tumor microenvironment. t-pHUDs also effectively suppressed cancer cell migration and vascular endothelial growth factor (VEGF) expression in response to H2O2. In animal studies, t-pHUDs exhibited highly potent anticancer activity. Notably, t-pHUDs, with their ability to accumulate preferentially in tumors due to the p-selectin targeting, surpassed the therapeutic efficacy of equivalent DOX and pHU nanoparticles alone. What is more, t-pHUDs significantly suppressed VEGF expression in tumors and mitigated hepato- and cardiotoxicity of DOX. Given their cancer targeting ability, enhanced therapeutic efficacy and minimized off-target toxicity, t-pHUDs present an innovative and targeted approach with great translational potential as an anticancer therapeutic agent.

Nanoparticle/Engineered Bacteria Based Triple-Strategy Delivery System for Enhanced Hepatocellular Carcinoma Cancer Therapy.

New treatment modalities for hepatocellular carcinoma (HCC) are desperately critically needed, given the lack of specificity, severe side effects, and drug resistance with single chemotherapy. Engineered bacteria can target and accumulate in tumor tissues, induce an immune response, and act as drug delivery vehicles. However, conventional bacterial therapy has limitations, such as drug loading capacity and difficult cargo release, resulting in inadequate therapeutic outcomes. Synthetic biotechnology can enhance the precision and efficacy of bacteria-based delivery systems. This enables the selective release of therapeutic payloads in vivo. In this study, we constructed a non-pathogenic Escherichia coli (E. coli) with a synchronized lysis circuit as both a drug/gene delivery vehicle and an in-situ (hepatitis B surface antigen) Ag (ASEc) producer. Polyethylene glycol (CHO-PEG2000-CHO)-poly(ethyleneimine) (PEI25k)-citraconic anhydride (CA)-doxorubicin (DOX) nanoparticles loaded with plasmid encoded human sulfatase 1 (hsulf-1) enzyme (PNPs) were anchored on the surface of ASEc (ASEc@PNPs). The composites were synthesized and characterized. The in vitro and in vivo anti-tumor effect of ASEc@PNPs was tested in HepG2 cell lines and a mouse subcutaneous tumor model. The results demonstrated that upon intravenous injection into tumor-bearing mice, ASEc can actively target and colonise tumor sites. The lytic genes to achieve blast and concentrated release of Ag significantly increased cytokine secretion and the intratumoral infiltration of CD4/CD8+T cells, initiated a specific immune response. Simultaneously, the PNPs system releases hsulf-1 and DOX into the tumor cell resulting in rapid tumor regression and metastasis prevention. The novel drug delivery system significantly suppressed HCC in vivo with reduced side effects, indicating a potential strategy for clinical HCC therapy.

Chitosan functionalized doxorubicin loaded poly(methacrylamide) based copolymeric nanoparticles for enhanced cellular internalization and in vitro anticancer evaluation

Doxorubicin (Dox), a chemotherapeutic agent, encounters challenges such as a short half-life, dose-dependent toxicity, and low solubility. In this context, the present study involved the fabrication of N-(2-hydroxypropyl)methacrylamide (HPMA) and N-(3-aminopropyl)methacrylamide (APMA) bearing P(HPMA-s-APMA) copolymeric nanoparticles (P(HPMA-s-APMA) NPs) and their investigation for efficient delivery of Dox. Furthermore, the synthesized nanoparticles (NPs) were coated with chitosan (Cht) to generate positively charged nanoformulations. The prepared formulations were evaluated for particle size, morphology, surface charge analysis, percentage encapsulation efficiency (EE%), and drug release studies. The anticancer activity of Cht-P(HPMA-s-APMA)-Dox NPs was assessed in the HeLa cancer cell line. The prepared P(HPMA-s-APMA)-Dox NPs exhibited an average particle size of 240–250 nm. Chitosan decorated P(HPMA-s-APMA)-Dox NPs displayed a significant increase in particle size, and the zeta potential shifted from negative to positive. The EE% for Cht-P(HPMA-s-APMA)-Dox NPs was calculated to be 68.06 %. The drug release studies revealed a rapid release of drug from Cht-P(HPMA-s-APMA)-Dox NPs at pH 4.8 than pH 7.4, demonstrating the pH-responsiveness of nanoformulation. Furthermore, the cell viability assay and internalization studies revealed that Cht-P(HPMA-s-APMA)-Dox NPs had a high cytotoxic response and significant cellular uptake. Hence, the Cht-P(HPMA-s-APMA)-Dox NPs appeared to be a suitable nanocarrier for effective, and safe chemotherapy.

Glucose-Regulated Protein 78 Targeting ICG and DOX Loaded Hollow Fe3O4 Nanoparticles for Hepatocellular Carcinoma Diagnosis and Therapy.

Liver cancer is considered as the third leading cause of cancer-related deaths, with hepatocellular carcinoma (HCC) accounting for approximately 90% of liver cancers. Improving the treatment of HCC is a serious challenge today. The primary objective of this study was to construct SP94-Fe3O4@ICG&DOX nanoparticles and investigate their potential diagnosis and treatment effect benefits on HCC. Firstly, we synthesized and characterized SP94-Fe3O4@ICG&DOX nanoparticles and confirmed their in vitro release behavior, photothermal and photodynamic performance. Moreover, the in vivo imaging capability was also observed. Finally, the inhibitory effects on Hepa1-6 in vitro and in vivo were observed as well as biosafety. SP94-Fe3O4@ICG&DOX nanoparticles have a size of ~22.1 nm, with an encapsulation efficiency of 45.2% for ICG and 42.7% for DOX, showing excellent in vivo MPI and fluorescence imaging capabilities for precise tumor localization, and synergistic photo-chemotherapy (pH- and thermal-sensitive drug release) against tumors under irradiation. With the assistance of a fluorescence molecular imaging system or MPI scanner, the location and contours of the tumor were clearly visible. Under a constant laser irradiation (808 nm, 0.6 W/cm2) and a set concentration (50 µg/mL), the temperature of the solution could rapidly increase to ~45 °C, which could effectively kill the tumor cells. It could be effectively uptaken by HCC cells and significantly inhibit their proliferation under the laser irradiation (100% inhibition rate for HCC tumors). And most importantly, our nanoparticles exhibited favorable biocompatibility with normal tissues and cells. This versatile agent can serve as an intelligent and promising nanoplatform that integrates multiple accurate diagnoses, precise positioning of cancer tissue, and effective coordination with synergistic tumor photodynamic therapy.

Polypyrrole nanoparticles loaded with doxorubicin for pH-responsive combinational photothermal-chemotherapy of cancer cells

The combined treatment method integrated photothermal therapy (PTT) with chemotherapy is extremely promising owing to the synergistic therapeutic effect as compared to single PTT or chemotherapy. To facilitate more novel and facile photothermal-chemotherapy drugs as well as promote controllable combination therapy, we have developed a mild and facile method to fabricate polymer polypyrrole (PPy)-doxorubicin (DOX) nanoparticles (NPs) as pH-responsive drug nanocarriers for synergistic photothermal-chemotherapy. In the nanoplatform, poly-L-lysine (PLL)-modified PPy serves as the photothermal material, and (DOX) molecules are adopted as the chemotherapy agent. Based on the cross-linking reaction of glutaraldehyde, DOX molecules are flexibly and efficiently assembled on the surface of PLL-modified PPy NPs. The obtained PPy-DOX NPs possess high photothermal effect, superior loading capacity of DOX, and controlled drug release behavior. The combination photothermal-chemotherapy based on PPy-DOX NPs has significantly enhanced the antitumor therapy effect. In general, the designed PPy-DOX NPs may be a potential drug delivery nanoplatform for cancer combination therapy.

DEVELOPMENT AND EVALUATION OF DOXORUBICIN ANCHORED PLGA NANOPARTICLES AGAINST BREAST CANCER

The objective of this work was to design and develop Poly (D, L-Lactide-co-glycolide) (PLGA) nanoparticles (NPs) of Doxorubicin for the effective treatment of breast cancer. The nanoparticles (NPs) were optimized by applying a Box-Behnken design (BBD) using Design-Expert® Software and prepared using the double emulsification and precipitation method. Three independent factors such as PLGA 50:50 (A), PVA (B), stirring speed (C) were considered. Three dependent responses included entrapment efficiency (Response 1), particle size (Response 2) and Doxorubicin release at 10th hour (Response 3). ATR and DSC studies indicated compatibility between the drug and polymer. The morphological studies performed by SEM showed uniform and spherical shaped discrete particles with smooth surface and in a size range of 282.6 nm. X-ray diffraction was performed to confirm the crystalline nature of the drug after encapsulation. The NPs exhibited a zeta potential of 21.6 mV. In vitro release studies showed a drug release up to 10 hrs. The release kinetics study indicated first order kinetics while the release mechanism followed Higuchi model. The cell viability was found to be more than 80% after incubation with the DOX NPs for 24 h up to a concentration of 80 μg/ml. The DOX NPs treated MCF-7 displayed intrinsic cell damage and cell shrinkage as compared to the control group. It may be concluded from the present investigation that PLGA NPs bearing doxorubicin can effectively treat the breast cancer

The role of gold nanoparticles in anticancer activity

To enhance the cellular uptake and chemotherapeutic efficacy of a current chemotherapeutic medication, a nanoparticle drug carrier technology has been designed. Due to their distinctive electrical and optical characteristics, gold nanoparticles (Au NPs) have recently demonstrated intriguing medical and military uses. In the event that they come into touch with a biological system, little is known about their biocompatibility. Metallic nanoparticles have been successfully utilized for a kind of biological applications. A drug delivery system known as Au – PEG – PAMAM – DOX was produced by conjugating the dendrimer with the anti-cancer chemical doxorubicin (DOX) via an amide bond. The amount of DOX released from Au – PEG – PAMAM – DOX at a natural pH was negligible, but this amount significantly increased in an environment with a weak acidic milieu, according to studies on the release of medicines from acellular sources. A research into the intracellular release of the medication was carried out with the assistance of confocal laser scanning microscopy (CLSM). Recently conjugation to the nanosystem, In vitro viability experiments revealed an increase in the associated DOX cytotoxicity that could not be attributable to carrier components. This indicates that the effectiveness of the DOX was increased. In light of this, it has been hypothesized that the newly created pH-triggered multifunctional Au NPs- DOX nanoparticle system could pave the way for a viable platform for the intracellular delivery of a range of anticancer medicines. In the current study, the common Au NPs synthesis techniques and their well-established uses in diverse needs, particularly in biological sensing applications.

Complete breakdown of copper-free clickable doxorubicin nanoclusters for real-time tumor proliferation tracking

Size-dependent localization of nanoscale carriers is essential for enhancing therapeutic windows and minimizing side effects in anticancer therapy. Therefore, we prepared polymeric nanoparticle (NP) clusters that could be clicked in response to the surrounding enzyme levels in tumor tissues to accomplish diagnostic and therapeutic systems with a single nanocluster. Multiarmed poly(ethylene glycol) (PEG) was conjugated with multiple molecules of doxorubicin (DOX), and the longest arm was designed to be abolished in response to matrix metalloproteinase (MMP) levels. These PEG conjugates self-assembled into anticancer NPs, and PEG shells were peeled at high threshold MMP levels. These DOX NPs were copper-free clicked with azide-functionalized quantum dots in response to the surrounding MMP levels. Therefore, the fluorescence of the systems was quenched, which was dependent on the tumor cell types. Ex vivo experiments on harvested tumor tissues validated the correlation between fluorescence quenching and tumor weight, highlighting the potential of these NPs as tools for monitoring tumor progression and therapeutic efficacy.

Orange-derived extracellular vesicles nanodrugs for efficient treatment of ovarian cancer assisted by transcytosis effect

Extracellular vesicles (EVs) have recently received much attention about the application of drug carriers due to their desirable properties such as nano-size, biocompatibility, and high stability. Herein, we demonstrate orange-derived extracellular vesicles (OEV) nanodrugs (DN@OEV) by modifying cRGD-targeted doxorubicin (DOX) nanoparticles (DN) onto the surface of OEV, enabling significantly enhancing tumor accumulation and penetration, thereby efficiently inhibiting the growth of ovarian cancer. The obtained DN@OEV enabled to inducement of greater transcytosis capability in ovarian cancer cells, which presented the average above 10-fold transcytosis effect compared with individual DN. It was found that DN@OEV could trigger receptor-mediated endocytosis to promote early endosome/recycling endosomes pathway for exocytosis and simultaneously reduce degradation in the early endosomes-late endosomes-lysosome pathway, thereby inducing the enhanced transcytosis. In particular, the zombie mouse model bearing orthotopic ovarian cancer further validated DN@OEV presented high accumulation and penetration in tumor tissue by the transcytosis process. Our study indicated the strategy in enhancing transcytosis has significant implications for improving the therapeutic efficacy of the drug delivery system.

Biomimetic Boron Nitride Nanoparticles for Targeted Drug Delivery and Enhanced Antitumor Activity.

Boron nitride nanomaterials are being increasingly recognized as vehicles for cancer drug delivery that increase drug loading and control drug release because of their excellent physicochemical properties and biocompatibility. However, these nanoparticles are often cleared rapidly by the immune system and have poor tumor targeting effects. As a result, biomimetic nanotechnology has emerged to address these challenges in recent times. Cell-derived biomimetic carriers have the characteristics of good biocompatibility, long circulation time, and strong targeting ability. Here, we report a biomimetic nanoplatform (CM@BN/DOX) prepared by encapsulating boron nitride nanoparticles (BN) and doxorubicin (DOX) together using cancer cell membrane (CCM) for targeted drug delivery and tumor therapy. The CM@BN/DOX nanoparticles (NPs) were able to target cancer cells of the same type on its own initiative through homologous targeting of cancer cell membranes. This led to a remarkable increase in cellular uptake. In vitro simulation of an acidic tumor microenvironment could effectively promote drug release from CM@BN/DOX. Furthermore, the CM@BN/DOX complex exhibited an excellent inhibitory effect against homotypic cancer cells. These findings suggest that CM@BN/DOX are promising in targeted drug delivery and potentially personalized therapy against their homologous tumor.

NIR- and pH-responsive injectable nanocomposite alginate-graft-dopamine hydrogel for melanoma suppression and wound repair

Surgical excision, chemotherapy, and radiotherapy are the main approaches used for treating melanoma. Unfortunately, surgical excision usually inevitably causes large area skin defects. In addition, chemotherapy and radiotherapy are often accompanied by adverse reactions and multi-drug resistance. To overcome these limitations, a near-infrared (NIR)- and pH-responsive injectable nanocomposite hydrogel was developed using sodium alginate-graft-dopamine (SD) and biomimetic polydopamine-Fe(III)-doxorubicin nanoparticles (PFD NPs) for treating melanoma and promoting skin regeneration. Firstly, the SD/PFD hydrogel can precisely deliver anti-cancer agents to the tumor site to reduce its loss and off-target toxicity. Then, PFD can convert light into heat energy under NIR irradiation to kill cancer cells. Meanwhile, doxorubicin can be administered continuously and controllably by NIR- and pH-responsive. Additionally, the SD/PFD hydrogel can also relieve tumor hypoxia by decomposing endogenous hydrogen peroxide (H2O2) into oxygen (O2). Therefore, photothermal, chemotherapy, and nanozyme synergetic therapy resulted in the tumor suppression. Specifically, the SA-based hydrogel can kill bacteria, scavenge reactive oxygen species, promote the proliferation and migration of cells, and significantly accelerate skin regeneration. Therefore, this study provides a safe and effective strategy for melanoma treatment and wound repair.

The Role of Gold Nanoparticles/Au-PEG-PAMAM as Drug Delivery System for Treatment of Breast Cancer

To enhance the cellular uptake and chemotherapeutic efficacy of a current chemotherapeutic medication, a nanoparticle drug carrier technology has been designed. Due to their distinctive electrical and optical characteristics, gold nanoparticles (Au NPs) have recently demonstrated intriguing medical and military uses. In the event that they come into touch with a biological system, little is known about their biocompatibility. Metallic nanoparticles have been successfully utilized for a kind of biological applications. A drug delivery system known as Au – PEG – PAMAM – DOX was produced by conjugating the dendrimer with the anti-cancer chemical doxorubicin (DOX) via an amide bond. The amount of DOX released from Au – PEG – PAMAM – DOX at a natural pH was negligible, but this amount significantly increased in an environment with a weak acidic milieu, according to studies on the release of medicines from acellular sources. A research into the intracellular release of the medication was carried out with the assistance of confocal laser scanning microscopy (CLSM). Recently conjugation to the nanosystem, in vitro viability experiments revealed an increase in the associated DOX cytotoxicity that could not be attributable to carrier components. This indicates that the effectiveness of the DOX was increased. In light of this, it has been hypothesized that the newly created pH-triggered multifunctional Au NPs- DOX nanoparticle system could pave the way for a viable platform for the intracellular delivery of a range of anticancer medicines. In the current study, the common Au NPs synthesis techniques and their well-established uses in diverse needs, particularly in biological sensing applications.

Engineered bacteria combined with doxorubicin nanoparticles suppress angiogenesis and metastasis in murine melanoma models.

Methods capable of distributing antitumour therapeutics uniformly throughout an entire tumour and that can suppress metastasis at the same time, would be of great significance in improving cancer treatment. Bacteria-mediated synergistic therapies have been explored for better specificity, temporal and spatial controllability, as well for providing regulation of the immune microenvironment, in order to provide improved cancer treatment. To achieve this goal, here we developed an engineered bacteria delivery system (GDOX@HSEc) using synthetic biology and interfacial chemistry technologies. The engineered bacteria were concurrently modified to express heparin sulfatase 1 (HSulf-1) inside (HSEc), to attach doxorubicin-loaded glycogen nanoparticles (GDOX NPs) on their surface. Here we demonstrate that HSEc can actively target and colonise tumour sites resulting in HSulf-1 overexpression, thereby suppressing angiogenesis and metastasis. Simultaneously, the GDOX NPs were able to penetrate into tumour cells, leading to intracellular DNA damage. Our results confirmed that a combination of biotherapy and chemotherapy using GDOX@HSEc resulted in significant melanoma suppression in murine models, with reduced side effects. This study provides a powerful platform for the simultaneous delivery of biomacromolecules and chemotherapeutic drugs to tumours, representing an innovative strategy potentially more effective in treating solid tumours. STATEMENT OF SIGNIFICANCE: An original engineered bacteria-based system (GDOX@HSEc) was developed using synthetic biology and interfacial chemistry technologies to concurrently produce naturally occurring heparin sulfatase 1 (HSulf-1) inside and anchor doxorubicin-loaded glycogen nanoparticles on the surface. GDOX@HSEc allowed for combined local delivery of chemotherapeutic agents along with the enzymes and immunostimulatory bacterial adjuvants, which resulted in a synergistic action in the inhibition of tumour growth and metastasis. The study provides a potential therapeutic approach that allows therapeutic agents to be distributed in a spatiotemporally controllable manner in tumours for combinatorial enhanced therapy.

Nano-baicalein facilitates chemotherapy in breast cancer by targeting tumor microenvironment

Cancer-associated fibroblasts constitute a significant component in the tumor microenvironment, playing a pivotal role in tumor proliferation, invasion, migration, and metastasis. Consequently, therapy combining chemotherapeutic agents with tumor microenvironment (TME) modulators appears to be a promising avenue for cancer treatment. In this paper, a tumor microenvironment-based mPEG-PLGA nanoparticle loaded with baicalein (PMs-Ba) was constructed for the purpose of improving the tumor microenvironment in cases of triple-negative breast cancer. The results demonstrate that, on the one hand, PMs-Ba was able to inhibit the transforming growth factor β(TGF-β) signaling pathway to avoid the activation of cancer-associated fibroblasts (CAFs), thereby influencing the interstitial microenvironment of the tumor. On the other hand, the agent led to an increase in the infiltration of cytotoxic T cells, activating the tumor immune microenvironment. Meanwhile, in the murine breast cancer model, an intravenous injection of PMs-Ba combined with doxorubicin nanoparticles (PMs-ADM) significantly improved the antitumor effectiveness. These results suggest that baicalein encapsulated in nanoparticles may be a promising strategy for modulating the TME and for adjuvant chemotherapy, signifying a potential TME-remodeling nanoformulation that could enhance the antitumor efficacy of nanotherapeutics.