Semiconducting polymer nanoprodrugs enable tumor-specific therapy via sono-activatable ferroptosis.

Ferroptosis, a recently identified form of cell death, holds promise for cancer therapy, but concerns persist regarding its uncontrolled actions and potential side effects. Here, we present a semiconducting polymer nanoprodrug (SPNpro) featuring an innovative ferroptosis prodrug (DHU-CBA7) to induce sono-activatable ferroptosis for tumor-specific therapy. DHU-CBA7 prodrug incorporate methylene blue, ferrocene and urea bond, which can selectively and specifically respond to singlet oxygen (1O2) to turn on ferroptosis action via rapidly cleaving the urea bonds. DHU-CBA7 prodrug and a semiconducting polymer are self-assembled with an amphiphilic polymer to construct SPNpro. Ultrasound irradiation of SPNpro leads to the production of 1O2 via sonodynamic therapy (SDT) of the semiconducting polymer, and the generated 1O2 activated DHU-CBA7 prodrug to achieve sono-activatable ferroptosis. Consequently, SPNpro combine SDT with the controlled ferroptosis to effectively cure 4T1 tumors covered by 2-cm tissue with a tumor inhibition efficacy as high as 100 %, and also completely restrain tumor metastases. This study introduces a novel sono-activatable prodrug strategy for regulating ferroptosis, allowing for precise cancer therapy.

Strain surveillance during chemotherapy to improve cardiovascular outcomes: the SUCCOUR-MRI trial.

BACKGROUND AND AIMS: The detection of cancer therapy-related cardiac dysfunction (CTRCD) by reduction of left ventricular ejection fraction (LVEF) during chemotherapy usually triggers the initiation of cardioprotective therapy. This study addressed whether the same approach should be applied to patients with worsening of global longitudinal strain (GLS) without attaining thresholds of LVEF. METHODS: Strain sUrveillance during Chemotherapy for improving Cardiovascular Outcomes (SUCCOUR-MRI) was a prospective multicentre randomized controlled trial involving 14 sites. Of 355 patients receiving anthracyclines with normal baseline LVEF, 333 patients (age 59±13 years, 79% women) with at least one other CTRCD risk factor, able to undergo magnetic resonance imaging (MRI), GLS and 3D echocardiography were tracked over 12 months. A total of 105 patients (age 59±13 years, 75% women, 69% breast cancer) developing GLS-CTRCD (>12% relative reduction of GLS without a change in LVEF) between cardioprotection with neurohormonal antagonists versus usual care were randomized. The primary endpoint was 12-month change in MRI-LVEF; the secondary endpoint was MRI LVEF-defined CTRCD. RESULTS: During follow-up, 2 patients died and 2 developed heart failure. Most patients were randomized at 3 months (62%). Median doses of angiotensin inhibition/blockade and beta-blockade were 75% and 50% of respective targets; 21 (43%) had side-effects attributed to cardioprotection. Due to a smaller LVEF change from baseline with cardioprotection than usual care (-2.5±5.4% vs -5.6±5.9%, p=0.009), follow-up LVEF was higher after cardioprotection (59±5% vs 55±6%, p<0.0001). After adjustment for baseline LVEF, the mean (95% confidence interval) difference in the change in LVEF between the two groups was -3.6% (-1.8% to -5.5%, p<0.001). After cardioprotection, 1/49 patients developed 12-month LVEF-CTRCD, compared to 6/56 in usual care (p=0.075). GLS improved at 3 months post-randomization in the cardioprotection group, with little change with usual care. CONCLUSIONS: In patients with isolated GLS reduction after anthracyclines, cardioprotection is associated with better preservation of 12-month MRI-LVEF compared with usual care.

Enhancing access to expensive oncology medications in Pakistan: The critical role of pharmaceutical patient assistance programs in oncology care.

This article aims to explore the access of patient assistance program (PAPs) and the role of pharmacists in improving access to oncology care in Pakistan. PAPs aim to reduce the financial burden of cancer in Pakistan, with pharmaceutical companies providing medication at reduced costs, ranging from 33% to 90%. Pharmacists play a pivotal role in managing these programs, facilitating PAP, pharmacist, oncology care setting, cancer therapy more accessible to those who faced financial barriers to accessing them.

Cell blebbing novel therapeutic possibilities to counter metastasis.

Cells constantly reshape there plasma membrane and cytoskeleton during physiological and pathological processes (Hagmann et al. in J Cell Biochem 73:488-499, 1999). Cell blebbing, the formation of bulges or protrusions on the cell membrane, is related to mechanical stress, changes in intracellular pressure, chemical signals, or genetic anomalies. These membrane bulges interfere with the force balance of actin filaments, microtubules, and intermediate filaments, the basic components of the cytoskeleton (Charras in J Microsc 231:466-478, 2008). In the past, these blebs with circular structures were considered apoptotic markers (Blaser et al. in Dev Cell 11:613-627, 2006). Cell blebbing activates phagocytes and promotes the rapid removal of intrinsic compartments. However, recent studies have revealed that blebbing is associated with dynamic cell reorganization and alters the movement of cells in-vivo and in-vitro (Charras and Paluch in Nat Rev Mol Cell Biol 9:730-736, 2008). During tumor progression, blebbing promotes invasion of cancer cells into blood, and lymphatic vessels, facilitating tumor progression and metastasis (Weems et al. in Nature 615:517-525, 2023). Blebbing is a dominant feature of tumor cells generally absent in normal cells. Restricting tumor blebbing reduces anoikis resistance (survival in suspension) (Weems et al. in Nature 615:517-525, 2023). Hence, therapeutic intervention with targeting blebbing could be highly selective for proliferating pro-metastatic tumor cells, providing a novel therapeutic pathway for tumor metastasis with minimal side effects. Here, we review the association between cell blebbing and tumor cells, to uncover new research directions and strategies for metastatic cancer therapy. Finaly, we aim to identify the druggable targets of metastatic cancer in relation to cell blebbing.

Mitochondrial Transfer as a Strategy for Enhancing Cancer Cell Fitness:Current Insights and Future Directions.

It is now recognized that tumors are not merely masses of transformed cells but are intricately interconnected with healthy cells in the tumor microenvironment (TME), forming complex and heterogeneous structures. Recent studies discovered that cancer cells can steal mitochondria from healthy cells to empower themselves, while reducing the functions of their target organ. Mitochondrial transfer, i.e. the intercellular movement of mitochondria, is recently emerging as a novel process in cancer biology, contributing to tumor growth, metastasis, and resistance to therapy by shaping the metabolic landscape of the tumor microenvironment. This review highlights the influence of transferred mitochondria on cancer bioenergetics, redox balance and apoptotic resistance, which collectively foster aggressive cancer phenotype. Furthermore, the therapeutic implications of mitochondrial transfer are discussed, emphasizing the potential of targeting these pathways to overcome drug resistance and improve treatment efficacy.

Emerging roles of intratumor microbiota in cancer: tumorigenesis and management strategies.

The intricate interplay between the host and its microbiota has garnered increasing attention in the past decade. Specifically, the emerging recognition of microorganisms within diverse cancer tissues, previously presumed sterile, has ignited a resurgence of enthusiasm and research endeavors. Four potential migratory routes have been identified as the sources of intratumoral microbial "dark matter," including direct invasion of mucosal barriers, spreading from normal adjacent tissue, hematogenous spread, and lymphatic drainage, which contribute to the highly heterogeneous features of intratumor microbiota. Importantly, multitudes of studies delineated the roles of intratumor microbiota in cancer initiation and progression, elucidating underlying mechanisms such as genetic alterations, epigenetic modifications, immune dysfunctions, activating oncogenic pathways, and inducing metastasis. With the deepening understanding of intratumoral microbial composition, novel microbiota-based strategies for early cancer diagnosis and prognostic stratification continue to emerge. Furthermore, intratumor microbiota exerts significant influence on the efficacy of cancer therapeutics, particularly immunotherapy, making it an enticing target for intervention in cancer treatment. In this review, we present a comprehensive discussion of the current understanding pertaining to the developmental history, heterogeneous profiles, underlying originations, and carcinogenic mechanisms of intratumor microbiota, and uncover its potential predictive and intervention values, as well as several inevitable challenges as a target for personalized cancer management strategies.

ROS-Responsive and Self-Catalytic Nanocarriers for a Combination of Chemotherapy and Reinforced Ferroptosis against Breast Cancer.

Ferroptosis is an appealing cancer therapy strategy based on the H2O2-involved Fenton reaction to produce toxic •OH for lipid peroxidation. However, intracellular H2O2 is easily consumed and results in a deficient Fenton reaction. This obstacle can be overcome by traditional chemotherapeutic drugs for H2O2 supplements. Moreover, a recent work illustrated that dihydroartemisinin (DHA) could promote ferroptosis against tumoral cells, particularly in the presence of ferrous compounds. To achieve combined chemotherapy and ferroptosis, a nanocarrier (TKNPDHA-Fc) was constructed by using thioketal (TK)-bridged paclitaxel prodrug (PEG-TK-PTX) and ferrocene (Fc)-conjugated PEG-Fc, where DHA was encapsulated by a hydrophobic-hydrophobic interaction. Upon cellular uptake, TKNPDHA-Fc could facilitate PTX release through TK breakage under an excess H2O2 microenvironment. Owing to the loss of the hydrophobic PTX component, TKNPDHA-Fc underwent a rapid dissociation for improving DHA to act as a ferroptotic inducer along with Fe supplied from Fc. Moreover, both the chemotherapy-induced reactive oxygen species and the •OH produced from reinforced ferroptosis further stimulated the TK cleavage. The "self-catalytic" loop of TKNPDHA-Fc remarkably improved the antitumor performance in vivo via combined mechanisms, and its tumor inhibition rate reached 78.3%. This work highlights the contribution of ROS-responsive and self-catalytic nanoplatforms for enhancing the potential of combined chemotherapy and ferroptosis for cancer therapy in the future.

Nano- and Micro-Platforms in Therapeutic Proteins Delivery for Cancer Therapy: Materials and Strategies.

Proteins have emerged as promising therapeutics in oncology due to their great specificity. Many treatment strategies are developed based on protein biologics, such as immunotherapy, starvation therapy, and pro-apoptosis therapy, while some protein biologics have entered the clinics. However, clinical translation is severely impeded by instability, short circulation time, poor transmembrane transportation, and immunogenicity. Micro- and nano-particles-based drug delivery platforms are designed to solve those problems and enhance protein therapeutic efficacy. This review first summarizes the different types of therapeutic proteins in clinical and research stages, highlighting their administration limitations. Next, various types of micro- and nano-particles are described to demonstrate how they can overcome those limitations. The potential of micro- and nano-particles are then explored to enhance the therapeutic efficacy of proteins by combinational therapies. Finally, the challenges and future directions of protein biologics carriers are discussed for optimized protein delivery.

Gut microbiome influences efficacy of Endostatin combined with PD-1 blockade against colorectal cancer.

The combination of anti-angiogenic drugs and immune checkpoint inhibitors (ICIs) in the treatment of tumors is emerging as a way to improve ICIs-resistant tumor therapy. In addition, gut microbes (GMs) are involved in angiogenesis in the tumor microenvironment and are also associated with the antitumor function of immune checkpoint inhibitors. However, it is unclear whether gut microbes have a role in anti-tumor function in the combination of anti-angiogenic drugs and immune checkpoint inhibitors for cancer treatment. Endostatin, an angiogenesis inhibitor, has been widely used as an antiangiogenic therapy for cancer. We showed that combined therapy with an adenovirus encoding human endostatin, named Ad-E, and PD-1 blockade dramatically abrogated MC38 tumor growth. The structure of intestinal microbes in mice was changed after combination treatment. We found that the antitumor function of combination therapy was inhibited after the elimination of intestinal microbes. In mice with depleted microbiota, oral gavage of Bacteroides fragilis salvaged the antitumor effects of combination Ad-E and αPD-1 monoclonal antibody (mAb) to a certain extent. Further, Bacteroides fragilis could improve CD3+T cells, NK cells, and IFNγ+CD8+ T cells in the tumor microenvironment to inhibit tumor growth. Besides, Bacteroides fragilis might restore antitumor function by down-regulating isobutyric acid (IBA). Our results suggested that GMs may be involved in the combination of Ad-E and αPD-1 mAb for cancer treatment, which has oncological implications for tumor growth dynamics and cancer immune surveillance.

New insights into the mechanisms of the extracellular matrix and its therapeutic potential in anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid cancer, and it has a poor prognosis and high probability of metastatic recurrence. The long-term survival of cancer cells depends on their ability to settle in a favorable environment. Cancer cells interact with other cells in the tumor microenvironment to shape the "soil" and make it suitable for cell growth by forming an extremely complex tumor ecosystem. The extracellular matrix (ECM) is an essential component of the tumor ecosystem, and its biological and mechanical changes strongly affect tumor invasion, metastasis, immune escape and drug resistance. Compared to normal tissues, biological processes, such as collagen synthesis and ECM signaling, are significantly activated in ATC tissues. However, how ATC triggers changes in the properties of the ECM and its interaction with the ECM remain poorly characterized. Therefore, an in-depth study of the regulatory mechanism of the abnormal activation of ECM signaling in ATC is highly important for achieving the therapeutic goal of exerting antitumor effects by destroying the "soil" in which cancer cells depend for survival. In this research, we revealed the aberrant activation state of ECM signaling in ATC progression and attempted to uncover the potential mechanism of action of ECM components in ATC, with the aim of providing new drug targets for ATC therapy.

P-glycoprotein (P-gp)-driven cancer drug resistance: biological profile, non-coding RNAs, drugs and nanomodulators.

Drug resistance has compromised the efficacy of chemotherapy. The dysregulation of drug transporters including P-glycoprotein (P-gp) can mediate drug resistance through drug efflux. In this review, we highlight the role of P-gp in cancer drug resistance and the related molecular pathways, including phosphoinositide 3-kinase (PI3K)-Akt, phosphatase and tensin homolog (PTEN) and nuclear factor-κB (NF-κB), along with non-coding RNAs (ncRNAs). Extracellular vesicles secreted by the cells can transport ncRNAs and other proteins to change P-gp activity in cancer drug resistance. P-gp requires ATP to function, and the induction of mitochondrial dysfunction or inhibition of glutamine metabolism can impair P-gp function, thus increasing chemosensitivity. Phytochemicals, small molecules and nanoparticles have been introduced as P-gp inhibitors to increase drug sensitivity in human cancers.

Tumor-Homing Antibody-Cytokine Fusions for Cancer Therapy.

Recombinant cytokine products have emerged as a promising avenue in cancer therapy due to their capacity to modulate and enhance the immune response against tumors. However, their clinical application is significantly hindered by systemic toxicities already at low doses, thus preventing escalation to therapeutically active regimens. One promising approach to overcoming these limitations is using antibody-cytokine fusion proteins (also called immunocytokines). These biopharmaceuticals leverage the targeting specificity of antibodies to deliver cytokines directly to the tumor microenvironment, thereby reducing systemic exposure and enhancing the therapeutic index. This review comprehensively examines the development and potential of antibody-cytokine fusion proteins in cancer therapy. It explores the molecular characteristics that influence the performance of these fusion proteins, and it highlights key findings from preclinical and clinical studies, illustrating the potential of immunocytokines to improve treatment outcomes in cancer patients. Recent advancements in the field, such as novel engineering strategies and combination strategies to enhance the efficacy and safety of immunocytokines, are also discussed. These innovations offer new opportunities to optimize this class of biotherapeutics, making them a more viable and effective option for cancer treatment. As the field continues to evolve, understanding the critical factors that influence the performance of immunocytokines will be essential for successfully translating these therapies into clinical practice.

Targeted Delivery of Circular Single-Stranded DNA Encoding IL-12 for the Treatment of Triple-Negative Breast Cancer.

Interleukin-12 (IL-12) is a critical cytokine with notable anticancer properties, including enhancing T-cell-mediated cancer cell killing, and curbing tumor angiogenesis. To date, many approaches are evaluated to achieve in situ overexpression of IL-12, minimizing leakage and the ensuing toxicity. Here, it is focused on circular single-stranded DNA (Css DNA), a type of DNA characterized by its unique structure, which could be expressed in mammals. It is discovered that Css DNA can induce sustained luciferase expression for half a year by intramuscular injection and showed effective antitumor results by intratumoral injection. Motivated by these findings, a folate-modified LNP system is now developed for the delivery of Css DNA expressing IL-12 for the therapy of 4T1 triple-negative breast cancer (TNBC). This delivery system effectively activates anti-cancer immune responses, slows tumor growth, significantly prolongs survival in animal models, and prevents tumor recurrence. After 6 months of long-term observation, the elevated level of IL-12 is still detectable in the lymph nodes and serum of the cured mice. This study highlights the long-term sustained expression capacity of Css DNA and its ability to inhibit recurrence, and the potential of tumor-targeted LNPs for Css DNA-based cancer therapy, providing a new insight into gene overexpression strategy.

Cell death pathways: molecular mechanisms and therapeutic targets for cancer.

Cell death regulation is essential for tissue homeostasis and its dysregulation often underlies cancer development. Understanding the different pathways of cell death can provide novel therapeutic strategies for battling cancer. This review explores several key cell death mechanisms of apoptosis, necroptosis, autophagic cell death, ferroptosis, and pyroptosis. The research gap addressed involves a thorough analysis of how these cell death pathways can be precisely targeted for cancer therapy, considering tumor heterogeneity and adaptation. It delves into genetic and epigenetic factors and signaling cascades like the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways, which are critical for the regulation of cell death. Additionally, the interaction of the microenvironment with tumor cells, and particularly the influence of hypoxia, nutrient deprivation, and immune cellular interactions, are explored. Emphasizing therapeutic strategies, this review highlights emerging modulators and inducers such as B cell lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), chloroquine, and innovative approaches to induce ferroptosis and pyroptosis. This review provides insights into cancer therapy's future direction, focusing on multifaceted approaches to influence cell death pathways and circumvent drug resistance. This examination of evolving strategies underlines the considerable clinical potential and the continuous necessity for in-depth exploration within this scientific domain.

Persistent Luminescence-Based Nanoreservoir for Benign Photothermal-Reinforced Nanozymatic Therapy.

Adjusting the catalytic activity of nanozymes for enhanced oncotherapy has attracted significant interest. However, it remains challenging to engineer regulatory tactics with a minimal impact on normal tissues. By exploiting the advantages of energy storage, photostimulated, and long afterglow luminescence of persistent nanoparticles (PLNPs), a persistent luminescence-based nanoreservoir was produced to improve its catalytic activity for benign oncotherapy. In the study, PLNPs in a nanoreservoir with the ability to store photons served as a self-illuminant to promote its peroxidase-like activity and therapeutic efficacy by persistently motivating its photothermal effect before and after external irradiation ceased. The photostimulated and persistent luminescence of PLNPs and spatiotemporal controllability of exogenous light jointly alleviated adverse effects induced by prolonged irradiation and elevated the catalytic capability of the nanoreservoir. Ultimately, the system fulfilled benign photothermal-intensive nanozymatic therapy. This work provides new insights into boosting the catalytic activity of nanozymes for secure disease treatment.

An update on small molecule compounds targeting synthetic lethality for cancer therapy.

Targeting cancer-specific vulnerabilities through synthetic lethality (SL) is an emerging paradigm in precision oncology. A SL strategy based on PARP inhibitors has demonstrated clinical efficacy. Advances in DNA damage response (DDR) uncover novel SL gene pairs. Beyond BRCA-PARP, emerging SL targets like ATR, ATM, DNA-PK, CHK1, WEE1, CDK12, RAD51, and RAD52 show clinical promise. Selective and bioavailable small molecule inhibitors have been developed to induce SL, but optimization for potency, specificity, and drug-like properties remains challenging. This article illuminated recent progress in the field of medicinal chemistry centered on the rational design of agents capable of eliciting SL specifically in neoplastic cells. It is envisioned that innovative strategies harnessing SL for small molecule design may unlock novel prospects for targeted cancer therapeutics going forward.

Variability in Kidney Cancer Treatment and Survival in England: Results of a National Cohort Study.

AIMS: To establish whether there are geographic differences in treatments and outcomes for patients with kidney cancer (KC) in England which could potentially be improved by the creation of national guidelines. MATERIALS AND METHODS: A multidisciplinary group convened by the charity Kidney Cancer UK developed Quality Performance Indicators (QPIs) for the treatment of KC. Adherence to these QPIs was reported for all patients with a histological diagnosis of KC diagnosed in England between 2017 and 2018. Utilising data extracted from national datasets, logistic and linear probability models were used to estimate geographic variation in the delivery of surgery and systemic anti-cancer therapy at Cancer Alliance and NHS trust levels. Results were adjusted for a priori confounders, including age at diagnosis, area deprivation of residence, and Charlson Comorbidity Index. Differences in overall survival are reported. RESULTS: The cohort comprised 18,640 tumours in 18,421 patients. Of tumours diagnosed, median patient age was 68 (interquartile range 58-77) years and 63.4% were in males. When stratified by Cancer Alliance, the proportions of T1a/T1b/N0/M0 KC that had radical nephrectomy (RN), nephron sparing surgery or ablation ranged from 53.3% (95% CI [48.7, 57.8]) to 80.3% (95% CI [73.0, 86.0]). For stage T1b-3 cancers, the proportion that received RN ranged from 65.6% (95% CI [60.3, 70.5]) to 77.3% (95% CI [72.1, 81.7]). Patients with M0 (n = 12,365) and M1 KC (n = 3312) at diagnosis had 24-month survival of 87.5% and 25.1%, respectively. Of patients diagnosed with M1 KC, 50.3% received systemic anti-cancer therapy, ranging from 39.7% (95% CI [33.7, 46.1]) to 70.7% (95% CI [59.6, 79.8]) between Cancer Alliances. The six-month survival of these patients was 77.4% compared to 27.6% for those that did not receive SACT. CONCLUSION: These major geographical differences in surgical and systemic therapy practice have led to national guideline development.

Injectable Mechanophore Nanoparticles for Deep-Tissue Mechanochemical Dynamic Therapy.

Photodynamic therapy (PDT) and sonodynamic therapy (SDT), using nonionizing light and ultrasound to generate reactive oxygen species, offer promising localized treatments for cancers. However, the effectiveness of PDT is hampered by inadequate tissue penetration, and SDT largely relies on pyrolysis and sonoluminescence, which may cause tissue injury and imprecise targeting. To address these issues, we have proposed a mechanochemical dynamic therapy (MDT) that uses free radicals generated from mechanophore-embedded polymers under mechanical stress to produce reactive oxygen species for cancer treatment. Yet, their application in vivo is constrained by the bulk form of the polymer and the need for high ultrasound intensities for activation. In this study, we developed injectable, nanoscale mechanophore particles with enhanced ultrasound sensitivity by leveraging a core-shell structure comprising silica nanoparticles (NPs) whose interfaces are linked to polymer brushes by an azo mechanophore moiety. Upon focused ultrasound (FUS) treatment, this injectable NP generates reactive oxygen species (ROS), demonstrating promising results in both an in vitro 4T1 cell model and an in vivo mouse model of orthotopic breast cancers. This research offers an alternative therapy technique, integrating force-responsive azo mechanophores and FUS under biocompatible conditions.

Harnessing nanomaterials for copper-induced cell death.

Copper (Cu), an essential micronutrient with redox properties, plays a pivotal role in a wide array of pathological and physiological processes across virtually all cell types. Maintaining an optimal copper concentration is critical for cellular survival: insufficient copper levels disrupt respiration and metabolism, while excess copper compromises cell viability, potentially leading to cell death. Similarly, in the context of cancer, copper exhibits a dual role: appropriate amount of copper can promote tumor progression and be an accomplice, yet beyond befitting level, copper can bring about multiple types of cell death, including autophagy, apoptosis, ferroptosis, immunogenic cell death, pyroptosis, and cuproptosis. These forms of cell death are beneficial against cancer progression; however, achieving precise copper regulation within tumors remains a significant challenge in the pursuit of effective cancer therapies. The emergence of nanodrug delivery systems, distinguished by their precise targeting, controlled release, high payload capacity, and the ability to co-deliver multiple agents, has revitalized interest in exploiting copper's precise regulatory capabilities. Nevertheless, there remains a dearth of comprehensive review of copper's bidirectional effects on tumorigenesis and the role of copper-based nanomaterials in modulating tumor progression. This paper aims to address this gap by elucidating the complex role in cancer biology and highlighting its potential as a therapeutic target. Through an exploration of copper's dualistic nature and the application of nanotechnology, this review seeks to offer novel insights and guide future research in advancing cancer treatment.