Cancer Therapy Research Articles

PHF12 regulates HDAC1 to promote tumorigenesis via EGFR/AKT signaling pathway in non-small cell lung cancer

BackgroundLung cancer stands as the second most prevalent malignant neoplasm worldwide. Addressing the underlying mechanisms propelling the progression of non-small cell lung cancer is of paramount importance. In this study, we have elucidated the pivotal role of PHF12 in this context.Materials and methodsWe harnessed clinical lung cancer tissue samples and non-small cell lung cancer cell lines to discern the expression pattern of PHF12. In vitro assays probing cell proliferation were conducted to substantiate the functional impact of PHF12. Furthermore, an in vivo Xenograft model was employed to dissect the role of PHF12. Employing ChIP assays and qRT-PCR, we delved into the intricate binding dynamics between PHF12 and HDAC1. Mechanistic insights into the PHF12-HDAC1 axis in lung cancer progression were pursued via RNA-seq and GSEA analyses.ResultsNotably, PHF12 exhibited a substantial upregulation within tumor tissue, concomitant with its correlation to HDAC1. The trilogy of cell proliferation assays, transwell assays, and the Xenograft model collectively underscored the promoting influence of PHF12 on lung cancer proliferation, both in vitro and in vivo. The ChIP assay unveiled the transcriptional regulatory role of PHF12 in governing HDAC1 expression. This correlation extended to both mRNA and protein levels. PHF12 promotes NSCLC progression through regulating HDCA1 expression. Intriguingly, the rescue of function within NSCLC cell lines post PHF12 knockdown was achievable through HDAC1 overexpression. Additionally, our findings unveiled the capacity of the PHF12-HDAC1 axis to activate the EGFR/AKT signaling pathway, thereby further corroborating its significance in lung cancer progression.ConclusionOur study identified PHF12 as an oncogenic role in lung cancer proliferation and migration for the first time. PHF12 transcriptionally regulate HDAC1 and activate EGFR/AKT signaling pathway in NSCLC progression. PHF12 may serve as an important target in lung cancer therapy.

Targeted cancer therapy: the initial high concentration may slow down the selection for resistance.

Unfortunately, any targeted therapy is, always, started with low levels of the drug in the organism, selecting for drug resistance. One should propose that initial drug levels must be maximized, and durations may be minimized, ideally, as portions of preemptive combination of targeted drugs.

Extended dipeptide composition framework for accurate identification of anticancer peptides

The identification of anticancer peptides (ACPs) is crucial, especially in the development of peptide-based cancer therapy. The classical models such as Split Amino Acid Composition (SAAC) and Pseudo Amino Acid Composition (PseAAC) lack the incorporation of feature representation. These advancements improve the predictive accuracy and efficiency of ACP identification. Thus, the effort of this research is to propose and develop an advanced framework based on feature extraction. Thus, to achieve this objective herein we propose an Extended Dipeptide Composition (EDPC) framework. The proposed EDPC framework extends the dipeptide composition by considering the local sequence environment information and reforming the CD-HIT framework to remove noise and redundancy. To measure the accuracy, we have performed several experiments. These experiments were employed using four famous machine learning (ML) algorithms named; Support Vector Machine (SVM), Decision Tree (DT), Random Forest (RF), and K Nearest Neighbor (KNN). For comparisons, we have used accuracy, specificity, sensitivity, precision, recall, and F1-Score as evaluation criteria. The reliability of the proposed framework is further evaluated using statistical significance tests. As a result, the proposed EDPC framework exhibited enhanced performance than SAAC and PseAAC, where the SVM model delivered the highest accuracy of 96. 6% and significant enhancements in specificity, sensitivity, precision, and F1-score over multiple datasets. Due to the incorporation of enhanced feature representation and the incorporation of local and global sequence profiles proposed EDPC achieves higher classification performance. The proposed frameworks can deal with noise and also duplicating features. These are accompanied by a wide range of feature representations. Finally, our proposed framework can be used for clinical applications where ACP identification is essential. Future works will include extending to a larger variety of datasets, incorporating tertiary structural information, and using deep learning techniques to improve the proposed EDPC.

Theranostic dye entrapped in an optimized blended-polymer matrix for effective photodynamic inactivation of diseased cells.

Despite the wide range of treatment options available for cancer therapy, including chemotherapy, radiation therapy, and surgical procedures, each of these treatments has a different side-effect profile and leaves the patient with no option but to choose. Due to their insensitivity and nonspecificity, conventional treatments damage normal cells together with cancer cells. In recent years, a significant amount of attention has been focused on photodynamic therapy (PDT) as a treatment for cancer and drug-resistant microbes. An activated photosensitizer is used as a part of the procedure along with oxygen molecules and a specific wavelength of light belonging to the visible or NIR spectral zone. A light-sensitive laser dye, rhodamine 6G (R6G), was used in the present study as a photosensitizer, taking a challenge to improve the aqueous solubility and ROS quantum yield using optimum concentration (160mg/ml) of chitosan-alginate (Cs-Alg) blended polymeric nanoformulations. As evidenced by steady-state spectrophotometric and fluorometric measurements, ROS quantum yield increases three-fold over aqueous solution along with solubility gaining that was validated by PDT experiment using human epithelial carcinoma (KB) cell line. Phantom optical imaging was taken using the IVIS imaging system to establish the formulations as a fluorescence-based optical contrast agent, and zebrafish embryos were used to establish their safe in vivo use. The release profile of R6G was fitted using kinetic models, which followed the Non-Fickian kinetic profile. In conclusion, we recommend the formulations as a potential theranostic agent that will aid in PDT-based therapy in conjunction with optical imaging-based diagnosis.

Ammonia borane-based targets for new developments in Laser-Driven proton boron fusion

Nuclear fusion reactions involving protons and boron-11 nuclei are sparking increasing interest thanks to advancements in pulsed laser technology. This type of reaction holds potential for a wide array of applications, from controlled nuclear fusion to radiobiology and cancer therapy. Following this motivation, novel solid ammonia borane samples are being developed as target material for proton-boron (pB) nuclear fusion. After being synthesized and shaped, these samples are being tested for the first time in a laser-plasma pB fusion experiment. An experimental campaign is focusing on surface chemical/physical analysis to characterize such samples in terms of composition of B and H, precursors of the pB fusion nuclear reaction, thus having a key impact on the yield of the generated nuclear products, i.e., alpha particles. A follow-up experiment is being conducted using an 8 J, 800 fs laser pulse with an intensity of 2 × 1019 W cm−2 to irradiate the targets, generating ∼ 108 alpha particles per steradian. The alpha particle energy range (2–6 MeV) and normalized yield per laser energy of up to (6 × 107 J/sr) is comparable with the best previous alpha particle yields found in literature, therefore paving the way for a yet unexplored category of pB fusion targets.

Spiky tubular nanoparticles with low protein corona can realize efficient and non-destructive penetration through endothelial barrier

Upon intravascular applications, i.e., cancer treatment, nanoparticles (NPs) are required to deliver through blood circulation, sustain serum protein interactions, before they penetrate the blood vessels and reach targeted sites for payload drug release. For a delivery process as such, it is elusive and difficult to comprehend the morphological change of NP surface and evaluate associated effects on its targeted delivery. Herein, we used silica NPs with different surface modifications to demonstrate the morphological impact of NPs during the application of the NP-blood protein interaction, vascular endothelial cell penetration, subsequent targeted delivery and photodynamic therapy efficacy and the morphology were designed for pursuing high drug loading capacity. Compared to solid and mesoporous NPs, we found the spiky tubular NPs facilitated to reserve the NPs' antifouling properties (or shedding of “protein corona”), promoted better endothelial penetration and less destruction in vitro and in vivo. This could be attributed to that those multiple spikes on spiky tubular NPs limited the NP-protein interaction area and promoted the NP-protein steric hindrance. Further in molecular simulations, we determined that the spiky tubular morphological modification on NPs enhanced the interaction free energy, while it lowered the amino acids number and the subsequent frequency in contacting with VE-cadherin of endothelia. As a result, these NPs have advantages in mitigating damages to VE-cadherin stability and endothelial cell integrity. Our finding here suggests that we could exploit the surface morphological modification to design spiky tubular NPs, to improve the NP delivery efficiency while prohibiting the leakiness of vascular endothelial microenvironment, particularly relevant for tumor migration during nanomedicine applications in cancer therapy.

Antibody-drug conjugates in cancer therapy: mechanisms and clinical studies.

Antibody-drug conjugates (ADCs) consist of monoclonal antibodies that target tumor cells and cytotoxic drugs linked through linkers. By leveraging antibodies' targeting properties, ADCs deliver cytotoxic drugs into tumor cells via endocytosis after identifying the tumor antigen. This precise method aims to kill tumor cells selectively while minimizing harm to normal cells, offering safe and effective therapeutic benefits. Recent years have seen significant progress in antitumor treatment with ADC development, providing patients with new and potent treatment options. With over 300 ADCs explored for various tumor indications and some already approved for clinical use, challenges such as resistance due to factors like antigen expression, ADC processing, and payload have emerged. This review aims to outline the history of ADC development, their structure, mechanism of action, recent composition advancements, target selection, completed and ongoing clinical trials, resistance mechanisms, and intervention strategies. Additionally, it will delve into the potential of ADCs with novel markers, linkers, payloads, and innovative action mechanisms to enhance cancer treatment options. The evolution of ADCs has also led to the emergence of combination therapy as a new therapeutic approach to improve drug efficacy.

Bacterial surface derived extracellular vesicles: A ground‐breaking approach in cancer therapy

AbstractConventional cancer therapies are often limited by inherent and acquired drug resistance, non‐specific toxicity, and suboptimal drug delivery. Bacterial extracellular vesicles (BEVs), including outer membrane vesicles and membrane vesicles, present a novel therapeutic strategy for cancer treatment. BEVs were found in both Gram‐negative and Gram‐positive bacteria. This article provides a classified investigation of the therapeutic potential of BEVs in cancer treatment. We discuss the molecular mechanisms underlying their observed anti‐tumor effects, including the induction of apoptosis in cancer cells, suppression of angiogenesis within the tumor microenvironment, and stimulation of both innate and adaptive anti‐tumor immune responses. Moreover, BEVs being biocompatible opens avenue for targeted drug delivery systems, potentially improving the therapeutic index of conventional chemotherapeutics. Challenges to clinical translation, such as BEV heterogeneity and potential immunogenicity, are addressed. We also explore future directions for research and development, comprehensively highlighting how BEVs transform the landscape of precision oncology and cancer treatment, eventually improving patient outcomes.

MiR-3195inhibits non-small cell lung cancer malignant behaviors along with cisplatin resistance through targetingPFKFB4.

Chemotherapy presents the main therapy of non-small cell lung cancer (NSCLC). Nevertheless, cisplatin-based therapy can be limited by drug resistance. MicroRNA (miRNA) possesses a vital regulatory function in modulating the progression as well as cisplatin resistance of NSCLC, but how miR-3195 influences NSCLC is obscure. In this work, it was discovered that miR-3195 presented definite down-regulation in NSCLC cells. Gain-of function assays revealed that overexpressing miR-3195 hindered NSCLC cell proliferation together with migration whereas induced cell apoptosis. Mechanically, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4) presented the target gene of miR-3195 and was high-expressed in NSCLC cells. The repressive impacts of overexpressing miR-3195 on NSCLC cells malignant behaviors were reversed via PFKFB4 elevation. Additionally, elevated miR-3195 expression reduced cisplatin resistance of NSCLC both in vitro as well as in vivo. PFKFB4 elevation could offset the reduced cisplatin resistance caused by miR-3195 overexpression in NSCLC cells. In conclusion, this work clarified miR-3195 repressed NSCLC cell proliferation, migration, as well as cisplatin resistance by modulating PFKFB4. Our study might provide a promising clue to promote the anti-tumor effects of chemotherapy.

68Ga/177Lu-Labeled Bivalent Agents for Targeting Hypoxia and PSMA-Binding in Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is an excellent target for cancer detection and therapy. Hypoxia is prevalent in solid tumors, and various nitroimidazole (NI) radioligands can be trapped inside hypoxic cells for diagnosis and therapy. To enhance tumor uptake and retention, we designed bivalent agents (compounds 1-8) incorporating a hypoxia-sensitive NI-moiety and a PSMA-targeting group. Ligands 1-8 were successfully prepared and labeled with 68Ga or 177Lu. Among them, [68Ga]Ga-8 ([68Ga]Ga-AAZTA-NI-PSMA-093) demonstrated significantly higher cellular accumulation under hypoxic conditions than under normoxic conditions, suggesting hypoxia-selective trapping by the introduction of NI group. PET/CT imaging at 60 min postinjection of [68Ga]Ga-8 revealed high tumor uptake (SUVmax: 10.68%ID/mL) in the tumor-bearing mice model. SPECT/CT imaging of [177Lu]Lu-8 at 24 and 48 h postinjection demonstrated excellent accumulation and retention. Preliminary studies indicate that [68Ga]Ga/[177Lu]Lu-8 may be promising bivalent agents targeting hypoxia and PSMA binding for diagnosis and radiotherapy.

Harnessing Dual Phototherapy and Immune Activation for Cancer Treatment: The Development and Application of BODIPY@F127 Nanoparticles.

Conventional phototherapeutic agents are typically used in either photodynamic therapy (PDT) or photothermal therapy (PTT). However, efficacy is often hindered by hypoxia and elevated levels of heat shock proteins in the tumor microenvironment (TME). To address these limitations, a formylated, near-infrared (NIR)-absorbing and heavy-atom-free Aza-BODIPY dye is presented that exhibits both type-I and type-II PDT actions with a high yield of reactive oxygen species (ROS) and manifests efficient photothermal conversion by precise adjustments to the conjugate structure and electron distribution, leading to a large amount of ROS production even under severe hypoxia. To improve biosafety and water solubility, the dye with an amphiphilic triblock copolymer (Pluronic F-127), yielding BDP-6@F127 nanoparticles (NPs) is coated. Furthermore, inspired by the fact that phototherapy triggers the release of tumor-associated antigens, a strategy that leverages potential immune activation by combining PDT/PTT with immune checkpoint blockade (ICB) therapy to amplify the systemic immune response and achieve the much-desired abscopal effect is developed. In conclusion, this study presents a promising molecular design strategy that integrates multimodal therapeutics for a precise and effective approach to cancer therapy.

A tumor microenvironment-activated near-infrared photosensitizer enable efficient photodynamic therapy of breast tumor

As an emerging cancer therapy with high selectivity, minimally invasive and low side effects, photodynamic therapy (PDT) has become the focus of current researches. The breast cancer is a malignant tumor with the highest incidence in women. Thus, it is valuable for improving its treatment efficiency to construct efficient photosensitizer. To this end, we engineered a high stable near-infrared photosensitizer NPA-NH2 based on “step by step” strategy. By modifying the optically tunable amino group of NPA-NH2, a peroxynitrite (ONOO-) activated NPA-ONOO- theranostic agent with a new trifluoromethylsulfonamide recognization site was designed and synthesized. It possessed a good singlet oxygen-generating ability after ONOO- activation under 660 nm light, and a high sensitivity (limit of detection: 0.038 μM) and selectivity respond toward ONOO- in buffer solution. The theranostic agent was able to specially monitor ONOO- in tumor cells. Furthermore, we have succeeded in applying the NPA-ONOO- for efficient and precise photodynamic therapy of breast cancer cells and tumors in vivo. This work provides a new way for the design of highly stable photosensitizers and a reliable tool for effective treatment of breast tumors.

Recent Advances in Biomacromolecule‐Reinforced 2D Material (2DM) Hydrogels: From Interactions, Synthesis, and Functionalization to Biomedical Applications

AbstractRegenerative biomedicine has emerged as a forefront area in medical research, heralding a new era of therapeutic strategies. This review delineates the integration of 2D materials (2DMs) within the area of biomedical engineering, leveraging their superior physicochemical attributes for enhance biomedical outcomes. The synergistic interaction between biomacromolecules and 2DMs is explored, demonstrating their potential to mitigate the limitations inherent to each while simultaneously augmenting their beneficial properties. In particular, incorporating 2DMs into hydrogels highlights their capability to enhance the mechanical strength of hydrogels, providing a biomimetic scaffold for tissue engineering regeneration and cancer diagnosis and therapy. An overview of the synthetic methodologies are provided for 2DMs, elucidating their interaction dynamics with biomacromolecules. The review primarily concentrates on the applications of biomacromolecule‐reinforced 2DM hydrogels across various biomedical fields, including bone tissue engineering, wound healing, neural tissue engineering, cardiac tissue engineering, as well as in the delivery of drugs and genes, cancer therapy, and biosensing technologies. Finally, the review discusses the existing challenges and future outlook for developing and using biomacromolecule‐reinforced 2DM hydrogels, underlining their transformative potential in regenerative medicine.

IL-33 stimulates the anticancer activities of eosinophils through extracellular vesicle-driven reprogramming of tumor cells

Immune cell-derived extracellular vesicles (EV) affect tumor progression and hold promise for therapeutic applications. Eosinophils are major effectors in Th2-related pathologies recently implied in cancer. Here, we evaluated the anti-tumor activities of eosinophil-derived EV following activation with the alarmin IL-33. We demonstrate that IL-33-activated mouse and human eosinophils produce higher quantities of EV with respect to eosinophils stimulated with IL-5. Following incorporation of EV from IL-33-activated eosinophils (Eo33-EV), but not EV from IL-5-treated eosinophils (Eo5-EV), mouse and human tumor cells increased the expression of cyclin-dependent kinase inhibitor (CDKI)-related genes resulting in cell cycle arrest in G0/G1, reduced proliferation and inhibited tumor spheroid formation. Moreover, tumor cells incorporating Eo33-EV acquired an epithelial-like phenotype characterized by E-Cadherin up-regulation, N-Cadherin downregulation, reduced cell elongation and migratory extent in vitro, and impaired capacity to metastasize to lungs when injected in syngeneic mice. RNA sequencing revealed distinct mRNA signatures in Eo33-EV and Eo5-EV with increased presence of tumor suppressor genes and enrichment in pathways related to epithelial phenotypes and negative regulation of cellular processes in Eo33-EV compared to Eo5-EV. Our studies underscore novel IL-33-stimulated anticancer activities of eosinophils through EV-mediated reprogramming of tumor cells opening perspectives on the use of eosinophil-derived EV in cancer therapy.

Exploring the Role of Target Expression in Treatment Efficacy of Antibody-Drug Conjugates (ADCs) in Solid Cancers: A Comprehensive Review.

Antibody-drug conjugates (ADCs) offer a promising path for cancer therapy, leveraging the specificity of monoclonal antibodies and the cytotoxicity of linked drugs. The success of ADCs hinges on precise targeting of cancer cells based on protein expression levels. This review explores the relationship between target protein expression and ADC efficacy in solid tumours, focusing on results of clinical trials conducted between January 2019 and May 2023. We hereby highlight approved ADCs, revealing their effectiveness even in low-expressing target populations. Assessing target expression poses challenges, owing to variations in scoring systems and biopsy types. Emerging methods, like digital image analysis, aim to standardize assessment. The complexity of ADC pharmacokinetics, tumour dynamics, and off-target effects emphasises the need for a balanced approach. This review underscores the importance of understanding target protein dynamics and promoting standardized evaluation methods in shaping the future of ADC-based cancer therapies.

Design of Cell-Specific Targeting Peptides for Cancer Therapy

Design of Cell-Specific Targeting Peptides for Cancer Therapy

Delivery of 5-fluorouracil for cancer therapy using aptamer-based nonlinear hybridization chain reaction

5-Fluorouracil (5-FU) is a conventional nucleotide analogue used for cancer treatment. However, its clinical application faces challenges such as low stability and non-specific toxicity. With the remarkable advancements in DNA nanotechnology, DNA-based self-assembled nanocarriers have emerged as powerful tools for delivering nucleotide drugs. In this study, we have designed a non-linear hybrid chain reaction involving a fuel strand with AS1411 aptamer sequence to construct a dendritic structure capable of carrying 5-FU. This structure specifically targets cancer cells with overexpressed nucleolin on their surface, allowing the 5-FU to exert its anticancer effects and achieve therapeutic outcomes. Furthermore, we have also investigated the mechanistic action of this drug delivery system, aiming to establish a novel therapeutic platform for 5-FU treatment.

Transcriptomic analysis of MCF7 breast cancer cells treated with MGBs reveals a profound inhibition of estrogen receptor genes

Breast cancer poses a significant health risk worldwide. However, the effectiveness of current chemotherapy is limited due to increasing drug resistance and side effects, making it crucial to develop new compounds with novel mechanism of action that can surpass these limitations. As a consequence of their reversible and targeted mechanism, DNA minor groove binders (MGBs) are considered as a relatively safer and more effective alternative. In this study transcriptomic analysis was conducted to reveal the dysregulated genes and signaling pathways in MCF7 cancer cells following treatment with novel MGB ligands to gain insights into the mechanism of action of MGBs at the molecular level. The transcriptomic results were validated using real-time PCR. The findings of this study indicate that the investigated MGBs primarily inhibit the genes associated with the estrogen receptor. Remarkably ligand 5 showed downregulation of 34 out of the 35 genes regulated by estrogen receptor, highlighting its potential as a promising candidate for breast cancer therapy.

Single-Domain Antibodies as Antibody–Drug Conjugates: From Promise to Practice—A Systematic Review

Background: Antibody–drug conjugates (ADCs) represent potent cancer therapies that deliver highly toxic drugs to tumor cells precisely, thus allowing for targeted treatment and significantly reducing off-target effects. Despite their effectiveness, ADCs can face limitations due to acquired resistance and potential side effects. Objectives: This study focuses on advances in various ADC components to improve both the efficacy and safety of these agents, and includes the analysis of several novel ADC formats. This work assesses whether the unique features of VHHs—such as their small size, enhanced tissue penetration, stability, and cost-effectiveness—make them a viable alternative to conventional antibodies for ADCs and reviews their current status in ADC development. Methods: Following PRISMA guidelines, this study focused on VHHs as components of ADCs, examining advancements and prospects from 1 January 2014 to 30 June 2024. Searches were conducted in PubMed, Cochrane Library, ScienceDirect and LILACS using specific terms related to ADCs and single-domain antibodies. Retrieved articles were rigorously evaluated, excluding duplicates and non-qualifying studies. The selected peer-reviewed articles were analyzed for quality and synthesized to highlight advancements, methods, payloads, and future directions in ADC research. Results: VHHs offer significant advantages for drug conjugation over conventional antibodies due to their smaller size and structure, which enhance tissue penetration and enable access to previously inaccessible epitopes. Their superior stability, solubility, and manufacturability facilitate cost-effective production and expand the range of targetable antigens. Additionally, some VHHs can naturally cross the blood–brain barrier or be easily modified to favor their penetration, making them promising for targeting brain tumors and metastases. Although no VHH–drug conjugates (nADC or nanoADC) are currently in the clinical arena, preclinical studies have explored various conjugation methods and linkers. Conclusions: While ADCs are transforming cancer treatment, their unique mechanisms and associated toxicities challenge traditional views on bioavailability and vary with different tumor types. Severe toxicities, often linked to compound instability, off-target effects, and nonspecific blood cell interactions, highlight the need for better understanding. Conversely, the rapid distribution, tumor penetration, and clearance of VHHs could be advantageous, potentially reducing toxicity by minimizing prolonged exposure. These attributes make single-domain antibodies strong candidates for the next generation of ADCs, potentially enhancing both efficacy and safety.

Targeted codelivery of doxorubicin and oleanolic acid by reduction responsive hyaluronic acid-based prodrug nano-micelles for enhanced antitumor activity and reduced toxicity

Chemotherapy remains one of the most commonly used strategies in cancer treatment but suffers from damages to healthy tissues and organs. How to precisely co-deliver two or more drugs with different mechanisms of action to the tumors for synergistic function is a challenge for chemotherapy. Herein, Oleanolic acid (OA)-conjugated Hyaluronic acid self-assembled nano-micelles loaded with Doxorubicin (DOX) (HSO NPs/DOX) were constructed for CD44 positive cancer targeted codelivery of DOX and OA. HSO NPs/DOX exhibited reduction triggered drug release under high concentration of glutathione, more efficient uptake by 4T1 breast cancer cells than free DOX leading to higher cytotoxicity, pro-apoptotic, and migration inhibitory activities against 4T1 cells. The ex vivo biodistribution experiment demonstrated more HSO NPs/DOX were accumulated in the tumor tissues than free DOX and less in the non-tumor tissues after injections in 4T1 tumor bearing mice. More importantly, synergistic anti-tumor effects of DOX and OA were obtained using HSO NPs/DOX in 4T1 breast tumor-bearing mice and toxicity of DOX to liver and heart were circumvented through regulating the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Silent Information Regulator 1 (Sirt1) expressions. Taken together, HSO NPs/DOX may become a promising codelivery system for chemotherapeutics in cancer therapy.