Cancers Therapy Research Articles

Probiotics as a potential tool for gynecological cancers prevention and therapy suport

The human body is host to a variety of microbial species that are essential for maintaining general health. About nine percent of these microbial species inhabit the urogenital tract. It is therefore important to establish a symbiotic relationship between the host’s immune system and the microbiota in this region. Disruptions of this symbiosis can contribute to the development of pelvic inflammatory disease (PID), bacterial vaginosis (BV), vaginal candidiasis and/or even gynaecological cancers by promoting the proliferation of infectious agents. The chemotherapeutic agents currently used in cancer treatment are associated with undesirable side effects. Therefore, there is an urgent need for antitumor agents that have minimal toxicity compared to conventional treatments. Furthermore, the use of drugs to prevent or alleviate the side effects of cervical cancer treatment could significantly improve the quality of life of patients undergoing such therapy. In this review, we focus our attention on the potential efficacy of probiotics in both the prevention and therapeutic intervention of neoplasms affecting the genital tract.

Special Issue “Nanoplatforms Based Cancers Therapy”

Nanomedicine is now considered a hopeful strategy to efficiently target cancer cells and deliver, more specifically, the molecule of interest to the area to image and treat cells [...].

Nanoparticles as Physically- and Biochemically-Tuned Drug Formulations for Cancers Therapy.

Simple SummaryConventional antitumor drugs have limitations, including poor water solubility and lack of targeting capability, with consequent non-specific distribution, systemic toxicity, and low therapeutic index. Nanotechnology promises to overcome these drawbacks by exploiting the physical properties of diverse nanocarriers that can be linked to moieties with binding selectivity for cancer cells. The use of nanoparticles as therapeutic formulations allows a targeted delivery and a slow, controlled release of the drug(s), making them tunable modules for applications in precision medicine. In addition, nanoparticles are also being developed as cancer vaccines, offering an opportunity to increase both cellular and humoral immunity, thus providing a new weapon to beat cancer.Malignant tumors originate from a combination of genetic alterations, which induce activation of oncogenes and inactivation of oncosuppressor genes, ultimately resulting in uncontrolled growth and neoplastic transformation. Chemotherapy prevents the abnormal proliferation of cancer cells, but it also affects the entire cellular network in the human body with heavy side effects. For this reason, the ultimate aim of cancer therapy remains to selectively kill cancer cells while sparing their normal counterparts. Nanoparticle formulations have the potential to achieve this aim by providing optimized drug delivery to a pathological site with minimal accumulation in healthy tissues. In this review, we will first describe the characteristics of recently developed nanoparticles and how their physical properties and targeting functionalization are exploited depending on their therapeutic payload, route of delivery, and tumor type. Second, we will analyze how nanoparticles can overcome multidrug resistance based on their ability to combine different therapies and targeting moieties within a single formulation. Finally, we will discuss how the implementation of these strategies has led to the generation of nanoparticle-based cancer vaccines as cutting-edge instruments for cancer immunotherapy.

Homozygous Co-Deletion of Type I Interferons and CDKN2A Genes in Thoracic Cancers: Potential Consequences for Therapy.

Homozygous deletion (HD) of the tumor suppressor gene CDKN2A is the most frequent genetic alteration in malignant pleural mesothelioma and is also frequent in non-small cell lung cancers. This HD is often accompanied by the HD of the type I interferons (IFN I) genes that are located closed to the CDKN2A gene on the p21.3 region of chromosome 9. IFN I genes encode sixteen cytokines (IFN-α, IFN-β…) that are implicated in cellular antiviral and antitumor defense and in the induction of the immune response. In this review, we discuss the potential influence of IFN I genes HD on thoracic cancers therapy and speak in favor of better taking these HD into account in patients monitoring.

The anticancer effect of extract of medicinal mushroom Sanghuangprous vaninii against human cervical cancer cell via endoplasmic reticulum stress-mitochondrial apoptotic pathway

Ethnopharmacological relevanceSanghuangprous vaninii (Ljub.) L.W. Zhou & Y.C. Dai, known as “Sanghuang” in China, is mainly distributed in the northeast of China. As a traditional medicinal mushroom, “Sanghuang” is medicinally used for resolving the symptoms of gynecological tumors including vaginal bleeding, leucorrhea, abdominal pain and abdominal mass. This mushroom is potential for gynecological cancers therapy. However, there is a lack of scientific evidence on its anti-tumor activity against human cervical cancer, the most common gynecological cancer. Aim of the studyTo identify the anti-tumor potential of the extract of Sanghuangprous vaninii (ESV) on human cervical cancer SiHa cells, and explore detailed mechanisms of ESV inducing cancer cell death. Materials and methodsThe anti-proliferation effects were evaluated by Cell Counting Kit-8 (CCK8) assay. Transmission electron microscope was applied to determined the cellular ultrastructure changes. The cell cycle distribution, quantification of apoptotic cells, mitochondrial transmembrane potential, reactive oxygen species (ROS) level, and cytosolic calcium level were determined by flow cytometer. Western blot analysis was used to explore the alterations in the expression levels of endoplasmic reticulum stress-marked and apoptosis-related proteins. The in-vivo anti-tumor effect was identified by mouse xenograft model. ResultsESV significantly inhibited the proliferation of SiHa cells in vivo and vitro. Blocking cell cycle and causing cell apoptosis contributed to cell death induced by ESV. Mechanistically, ESV induced endoplasmic reticulum stress evidenced by the elevated expressions of GRP78 and CHOP, which accompanied by the release of calcium (Ca2+). The Ca2+ overload and oxidative stress facilitated the collapse of mitochondrial membrane potential and subsequently activated caspase-3 and -9, which eventually lead to cell apoptosis. ConclusionsOur results revealed that Sanghuangprous vaninii was effective against human cervical cancer SiHa cells in vitro and vivo. There is a promising potential that Sanghuangprous vaninii might be a candidate for cervical cancer therapy.

Molecular mechanism of the anticancer effect of sweet red pepper extract

Background: Having non-toxic anticancer agents are targeted by researcher in the biomedical field around the world. Cancer-fighting phytochemicals have been potentially identified in several medicinal plants for cancers therapy. Apoptosis paid a great promise to study mechanism of cancer treatment. Objectives: This study aimed to investigate the antioxidants activities of the aqueous ethanolic extract of sweet red pepper (Capsicum Spp.) and its effects on colorectal cancer cell lines (CaCO-2). Methods: Phytochemical constituents and anticancer efficacy of sweet red pepper extract were evaluated. The apoptotic mechanism of the extract was proved by using real time polymerase chain reaction (RT-PCR) for apoptotic related genes (Bax, caspase 3 and Bcl-2). Results: The results showed that sweet red pepper extracts exhibited powerful antioxidant activities. Moreover, this extract could trigger apoptosis in human colorectal tumor cells by overexpressing apoptotic genes (Bax and caspase 3) and down-expressing the anti-apoptotic Bcl-2 genes. Conclusion: The sweet red pepper extract could inhibit CaCO-2 cellular proliferation by inducing apoptosis due to their phytochemical contents.

Predicting the Efficacy and Safety of TACTICs (Tumor Angiogenesis-Specific CAR-T Cells Impacting Cancers) Therapy for Soft Tissue Sarcoma Patients.

Simple SummarySarcomas have few effective treatment options due to the rarity and diversity and have a high risk of recurrence and metastasis. Therefore, the development of new therapeutics that can meet their medical needs is required. Our adoptive immunotherapy strategy using T cells to express the chimeric antigen receptor (CAR) against vascular endothelial growth factor receptor 2 (VEGFR2), which is highly expressed on tumor vascular endothelial cells, has the potential to be a novel treatment against diverse sarcomas with abundant vascular invasion. Here, we optimized the manufacturing and transportation of anti-VEGFR2 CAR-mRNA-transfected T cells and collected information that allowed the extrapolation of their efficacy and safety potential for sarcoma patients. Our results support the development of a “first in humans” study to evaluate the potential of our anti-VEGFR2 CAR-T cell therapy as a new treatment option for sarcoma patients.Soft tissue sarcomas (STSs) are heterogeneous and aggressive malignancies with few effective therapies available. We have developed T cells expressing a vascular endothelial growth factor receptor 2 (VEGFR2)-specific chimeric antigen receptor (CAR) to establish a tumor angiogenesis-specific CAR-T cells impacting cancers (TACTICs) therapy. In this study, we optimized the manufacturing and transportation of mRNA-transfected anti-VEGFR2 CAR-T cells and collected information that allowed the extrapolation of the efficacy and safety potential of TACTICs therapy for STS patients. Although 5-methoxyuridines versus uridines did not improve CAR-mRNA stability in T cells, the utilization of CleanCap as a 5′ cap-structure extended the CAR expression level, increasing VEGFR2-specific cytotoxicity. Furthermore, 4 °C preservation conditions did not affect the viability/cytotoxicity of CAR-T cells, contrarily to a freeze-thaw approach. Importantly, immunohistochemistry showed that most of the STS patients’ specimens expressed VEGFR2, suggesting a great potential of our TACTICs approach. However, VEGFR2 expression was also detected in normal tissues, stressing the importance of the application of a strict monitoring schedule to detect (and respond to) the occurrence of adverse effects in clinics. Overall, our results support the development of a “first in humans” study to evaluate the potential of our TACTICs therapy as a new treatment option for STSs.

A TCM Formula YYWY Inhibits Tumor Growth in Non-Small Cell Lung Cancer and Enhances Immune-Response Through Facilitating the Maturation of Dendritic Cells.

In worldwide, lung cancer has a major socio-economic impact and is one of the most common causes of cancer-related deaths. Current therapies for lung cancer are still quite unsatisfactory, urging for alternative new treatments. Traditional Chinese Medicine (TCM) is currently increasingly popular and exhibits a complicated intervention in cancers therapy. In this study, we evaluated the anti-tumor effect and explored the mechanisms of a TCM formula Yangyinwenyang (YYWY) in non-small cell lung cancer (NSCLC) models. YYWY induced the apoptosis of lung cancer cells in vitro. In Lewis NSCLC-bearing mice model, YYWY significantly inhibited the tumor growth. Further, RNA-seq analysis and immunostaining of the tumor tissue implied the critical role of YYWY in the regulation of immune response, especially the dendritic cells (DCs) in the effect of YYWY. Therefore, we focused on DCs, which were the initiator and modulator of the immune response. YYWY facilitated the maturation of DCs through MAPK and NF-κB signaling pathways and promoted the release of the cytokines IFN-γ, interleukin (IL)-1β, IL-2, IL-12, and tumor necrosis factor (TNF)-α by DCs. Moreover, the YYWY-matured DCs enhanced the proliferation of T cells and promoted the differentiation of T cells into T helper Th1 and cytotoxic T cell (CTL). In addition, YYWY increased the ratio of Th1/Th2 (IFN-γ/IL-4 radio). Collectively, our findings clearly suggested that YYWY exerted an anti-tumor effect on NSCLC, at least partially through facilitating the mature DCs to activate the proliferation and differentiation of T cells.

New cancers therapy through targeting Aldo-keto reductase family 1 member B10 with miRNAs.

New cancers therapy through targeting Aldo-keto reductase family 1 member B10 with miRNAs.

Influence of MRI Examinations on Animal Welfare and Study Results.

Magnetic resonance imaging (MRI) is considered to be well tolerated by laboratory animals. However, no systematic study has been performed yet, proving this assumption. Therefore, the aim of this study was to investigate the possible effects of longitudinal native and contrast-enhanced (CE) 1-T and 7-T MRI examinations on mouse welfare as well as 4T1 breast cancers progression and therapy response. Forty-seven healthy and 72 breast cancer-bearing mice (4T1) were investigated. One-Tesla (ICON) and 7-T (Biospec) MRI measurements were performed thrice per week under isoflurane anesthesia in healthy BALB/c mice for 4 weeks and 3 times within 2 weeks in tumor-bearing animals. Animal welfare was examined by an observational score sheet, rotarod performance, heart rate measurements, and assessment of fecal corticosterone metabolites. Furthermore, we investigated whether CE-MRI influences the study outcome. Therefore, hemograms and organ weights were obtained, and 4T1 tumor growth, perfusion, immune cell infiltration, as well as response to the multikinase inhibitor regorafenib were investigated. Statistical comparisons between groups were performed using analysis of variance and Tukey or Bonferroni post hoc tests. Mice showed no alterations in the observational score sheet rating, rotarod performance, heart rate, and fecal corticosterone metabolites (P > 0.05) after repeated MRI at both field strengths. However, spleen weights were reduced in all healthy mouse groups that received isoflurane anesthesia (P < 0.001) including the groups investigated by 1-T and 7-T MRI (P = 0.02). Neither tumor progression nor response to the regorafenib treatment was affected by isoflurane anesthesia or CE-MRI monitoring. Furthermore, immunohistological tumor analysis did not indicate an effect of isoflurane and MRI on macrophage infiltration of tumors, perfusion of tumor vessels, and apoptotic cell rate (P > 0.05). Repeated MRI did not influence the welfare of mice and did not affect tumor growth and therapy response of 4T1 tumors. However, systemic immunological effects of isoflurane anesthesia need to be considered to prevent potential bias.

Recent Advances in Identifying Biomarkers and High-Affinity Aptamers for Gynecologic Cancers Diagnosis and Therapy.

Cancer is the uncontrollable abnormal division of cell growth, caused due to the varied reasons. Cancer can be expressed in any part of the body, and it is one of the death-causing diseases. Human reproductive organs are commonly damaged by cancer. In particular, the women reproductive system is affected by various cancers including ovarian, cervical, endometrial, vaginal, fallopian tube, and vulvar cancers. Identifying these cancers at earlier stages prevents the damage to the organs. Aptamer is the potential probe that can identify these cancers. Aptamer is an artificial antibody selected from the randomized library of molecules and has a high binding affinity to the target biomarker. Targeting cancers in the reproductive organs using aptamers showed an excellent efficiency of detection compared to other probes. Different aptamers have been generated against the gynaecological cancer biomarkers, which include HE4, CA125, VEGF, OCCA (for ovarian cancer), EGFR, FGFR1, K-ras (for endometrial cancer), HPV E-16, HPV E-7, HPV E-6, tyrosine, and kinase (for cervical cancer), which help to identify the cancers in woman reproductive organs. In this overview, the biomarkers for gynecologic cancers and the relevant diagnosing systems generated using the specific aptamers are discussed. Furthermore, the therapeutic applications of aptamer with gynaecological cancers are narrated.

Highly specific colon-targeted transformable capsules containing indomethacin immediate-release pellets for colon cancers therapy

Generally, definite intestine targeting and immediate drug releasing are both important for the treatment of colon cancer via oral administration of anti-cancer drugs. We developed a highly specific oral colon-targeted pulsatile capsule, based on the effective enzyme-responsive ‘pulse plug’, which can be degraded under mannanase abundant in colon. Indomethacin (IN) solid dispersion immediate-release pellets were filled in an insoluble capsule body, a guar gum-lactose-hydroxypropyl methylcellulose (HPMC) composed tablet was embedded on the top of capsule as the ‘pulse plug’, and then covered by enteric soluble cap. In this study, the influence of the proportion of guar gum/lactose/HPMC, the viscosity of HPMC, and the tablet weight on the degradation behaviour of the plug tablet was investigated. The drug-releasing profiles of those pulsatile capsules in different simulated colon medium verified the ‘pulse plug’ could realise the colon-targeted pulsatile drug-releasing. Furthermore, the rabbit pharmacokinetic experiments showed that the in vivo time lag of drug loaded pulsatile capsules was significantly extended to 5.61 ± 0.08 h (p<.01), compared with that (0.33 ± 0.47 h) of the marketed tablets (YUNPENG®). These results indicated that colon-targeted pulsatile capsules would be effective oral delivering system for colon cancers therapy.

Application of selective CDK4/6 inhibitors in solid cancers therapy

Cyclin-dependent kinase (CDK) inhibitors have been approved for the treatment of ER+ /HER2- advanced breast cancer, and preclinical study and clinical trials are under way for multiple solid cancers. CDK4/6 inhibitors have shown good efficacy for human solid cancers, and it′s future development direction are biomarkers, drug resis-tance and combined therapy in the future. Key words: Neoplasms; Cyclin-dependent kinases; Therapeutics; Cell cycle

Inhibition of PSMD4 blocks the tumorigenesis of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver with high mortality and frequent recurrence. Although various therapies provide potential cure for HCC patients, unfortunately the five-year survival rate of advanced HCC remains dismal. It is critical to explore the pathogenesis of HCC and identify novel biomarkers for early HCC diagnosis. PSMD4 is a major receptor of the 26S proteasome involved in ubiquitindependent and proteasome-mediated protein degradation. In our study, PSMD4 was overexpressed in HCC tissues and cell lines determined by Northern blot, western blot and immunohistochemistry. The silencing of PSMD4 blocked cell proliferation and tumor growth, induced cell apoptosis and inhibited the proteasome activity. Western blot results showed that the knockdown of PSMD4 blocked the expression of cyclooxygenase 2 (COX2), phosphorylated Sarcoma tyrosine kinase (P-SRC) and Bcl-2, but improved the levels of p53 and Bax in HCC, lung cancer, colorectal cancer, breast cancer and endometrial cancer cell lines. Taken together, these findings indicated that the subunit of 26S proteasome PSMD4 exerts as an oncogene in HCC and other cancers via regulating the expression p53, Bcl-2 and Bax. These findings enriched the pathogenesis of HCC, and provided a new biomarker for cancers diagnosis and a new target for cancers therapy.

Structure-Based Pharmacophore Modeling to Discover Novel CCR5 Inhibitors for HIV-1/Cancers Therapy

CC chemokine receptor 5 (CCR5), a member of G protein-coupled receptors (GPCRs), not only plays a significant role in inflammatory responses, but also correlates with HIV-1 infection and cancer progression. Recently, blocking of CCR5 has been considered as an effective strategy in HIV-1/cancers therapy. So far, only Maraviroc has been approved by FDA in 2007, while the other CCR5 inhibitors have failed in their clinical trials. In this study, a highly selective structure-based pharmacophore model was constructed, validated, and applied for virtual screening to retrieve novel CCR5 inhibitors from NCI database. Finally, one potential CCR5 inhibitor candidate, NSC13165, was identified after molecular docking, molecular dynamics (MD) simulations, binding free energy analyses and ADMET prediction. Docking and MD simulation results not only suggested that NSC13165 reserves the common binding mode of the most known CCR5 inhibitors, but also provided important insights toward the allosteric inhibition mechanism of CCR5. The results of binding free energy analyses indicated that the binding affinity of NSC13165 is much better than that of Maraviroc and that van der Waals interaction is the key driving force during the binding process. ADMET prediction suggested that NSC13165 exhibits very low risk of causing lethal side effects. Altogether, our results strongly suggest that NSC13165 has great potential to serve as a novel CCR5 inhibitor, which may be further tested in vitro/in vivo as a drug target for HIV-1/cancers therapy or be used as a lead compound for improving its efficacy through chemical modifications.

A novel series of napabucasin derivatives as orally active inhibitors of signal transducer and activator of transcription 3 (STAT3)

The transcription factor STAT3 is an attractive target for a variety of cancers therapy. Napabucasin, applied in phase III clinical trials for the treatment of a variety of cancers, was regarded as one of the most promising anticancer drug by targeting STAT3. Herein, a novel series of napabucasin derivatives were designed and synthesized, which presented a potent inhibitory activity on a variety of cancers cells. Among the derivatives compound 8q exhibited potent inhibitory activity on U251, HepG2, HT29 and CT26 cells with the IC50 values of 0.22, 0.49, 0.07 and 0.14 μM, respectively, which was over 10-fold more potent than napabucasin. Treatment with compound 8q decreased protein expression level of total STAT3 and p-STAT3Y705in vitro. The binding of compound 8q with STAT3 were further validated by electrophoretic mobility shift assay and surface plasmon resonance analysis. Compound 8q has a KD of 110.2 nM for full-length STAT3 recombinant protein. Moreover, the aqueous solubility of 8q was over 4.5-fold than that of napabucasin. In addition, compound 8qin vivo significantly reduced tumor growth compared to untreated mice, and exhibited good safety profile, indicating its great potential as an efficacious drug candidate for oncotherapy.

Incidence of Unlicensed and Off-Label Prescription in Urologic Cancers Therapy in Turkey: Assessment of Legislative and Regulatory Policy

Incidence of Unlicensed and Off-Label Prescription in Urologic Cancers Therapy in Turkey: Assessment of Legislative and Regulatory Policy

Down-regulation of intracellular anti-apoptotic proteins, particularly c-FLIP by therapeutic agents; the novel view to overcome resistance to TRAIL.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) is a member of the tumor necrosis factor (TNF) superfamily that induces apoptosis in different types of cancer cells via activation of caspase cascade. TRAIL interacts with its cognate receptors that placed on cancer cells surface, including TRAIL-R1 (death receptor 4, DR4), TRAIL-R2 (death receptor 5, DR5), TRAIL-R3 (decoy receptor 1, DcR1), TRAIL-R4 (decoy receptor 2, DcR2), and osteoprotegerin (OPG). Despite high apoptosis-inducing ability of TRAIL, various cancerous cells gain resistance to TRAIL gradually, and consequently TRAIL potential for apoptosis stimulation in these cells diminishes intensely. According to diverse ranges of examinations, intracellular anti-apoptotic proteins, such as cellular-FLICE inhibitory protein (c-FLIP), apoptosis inhibitors (IAPs), myeloid cell leukemia sequence 1 (MCL-1), BCL-2, BCL-XL, and survivin play key role in cancer cells resistance to TRAIL. These proteins attenuate cancer cells sensitivity to TRAIL via various functions, importantly through caspase cascade suppression. The c-FLIP avoids from caspase 8 activation by FADD via binding to caspase 8 cleavage of FADD. Moreover, it activates signaling pathways that involved in cancer cells survival and proliferation. Intriguingly, it appears that the down-regulation of intracellular anti-apoptotic proteins, particularly c-FLIP is effectiveness goal for TRAIL-resistant cancers therapy, because their up-regulation in association with poor prognosis has been observed in various types of TRAIL-resistant cancers. In this review, we tried to collect and examine investigations that researchers have been able to sensitize cancer cells to TRAIL through targeting of c-FLIP alone or with other intracellular anti-apoptotic proteins directly or indirectly. It seems that co-treatment of resistant cells by TRAIL with other therapeutic agents with the aim of intracellular anti-apoptotic proteins inhibition is hopeful and attractive approach to overcome various TRAIL-resistant cancers.

The silencing of replication protein A1 induced cell apoptosis via regulating Caspase 3

AimsGastrointestinal cancers are a kind of deadly malignancy afflicting close to a million peoples worldwide. 5-Fluorouracil (5-Fu) is a main chemotherapeutic agent for cancer treatment. However, prolonged exposure of 5-Fu to cancer cells may cause chemoresistance and decrease the therapeutic potential of 5-Fu. Main methodsReplication protein A (RPA) is a component of the origin recognition complex. In our study, we explored the role of RPA1 in hepatocellular carcinoma cell SMMC-7721, gastric cancer cell SGC-7901 and colorectal cancer HT-29 via lentiviral particles infection. Flow cytometry assay was used to examine the effect of RPA1 on cell proliferation, cell cycle and apoptosis. Western blot was employed to determine the role of RPA1 on Caspase 3 expression. Key findingsImmunohistochemstry results showed that RPA1 was highly expressed in colorectal cancer tissues. Only 5-Fu or the knockdown of RPA1 suppressed cell clone formation, induced cell cycle arrest at the G1 phase and promoted cell apoptosis by regulating the protein level of Caspase 3. And the combination of the application of 5-Fu and RPA1 silencing significantly enhanced the above effects. SignificanceRPA1 serves as an oncogene during gastrointestinal cancers progression. These studies reveal a new target for gastrointestinal cancers therapy, and the combination of 5-Fu and silencing of RPA1 provides a new attractive therapeutic measure for gastrointestinal cancers.

Reactive oxygen species-responsive nanoprodrug with quinone methides-mediated GSH depletion for improved chlorambucil breast cancers therapy

Prodrug-based stimuli-responsive vectors have emerged as highly promising platform. Inspired by the fact that antioxidant systems including glutathione (GSH) make cancer cells adapt to oxidative stress and play a role in the inactivation of alkylating agents like chlorambucil (CHL) inside tumor cells, while arylboronic acid could transform into GSH depleting agent quinone methide (QM) upon degradation by reactive oxygen species (ROS) over-expressed in tumor cells, a ROS-responsive nanoprodrug (denoted by PPAHC) of CHL was established by integrating CHL into diols-containing hydrophilic polymer with self-immolative linker 4-(hydroxymethyl)phenylboronic acid (HPBA). The prodrug could form core-shell nanoparticle and possess high stability during storage. Drug release profile of PPAHC nanoprodrug demonstrated that nature CHL could be quickly released from PPAHC nanoprodrug in the presence of hydrogen peroxide (H2O2). Moreover, PPAHC nanoprodrug showed improved therapeutic efficiency compared to CHL via anti-proliferative study and cell apoptosis assay. Further measurement of GSH content and ROS levels in tumor cells suggested that the synergistic impact resulted from QM-mediated GSH reduction and CHL-induced further oxidative stress insults to tumor cells. In vivo tumor suppression effect and biocompatibility indicated the superiorities of PPAHC nanoprodrug. Accordingly, PPAHC provides a new approach as a ROS-responsive CHL delivery system and has a great potential for cancer therapy.