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Chemotherapy has been widely applied in clinics. However, the therapeutic potential of chemotherapy against cancer is seriously dissatisfactory due to the nonspecific drug distribution, multidrug resistance (MDR) and the heterogeneity of cancer. Therefore, combinational therapy based on chemotherapy mediated by nanotechnology, has been the trend in clinical research at present, which can result in a remarkably increased therapeutic efficiency with few side effects to normal tissues. Moreover, to achieve the accurate pre-diagnosis and real-time monitoring for tumor, the research of nano-theranostics, which integrates diagnosis with treatment process, is a promising field in cancer treatment. In this review, the recent studies on combinational therapy based on chemotherapy will be systematically discussed. Furthermore, as a current trend in cancer treatment, advance in theranostic nanoparticles based on chemotherapy will be exemplified briefly. Finally, the present challenges and improvement tips will be presented in combination therapy and nano-theranostics.

On the 30 of January 2020, the World Health Organization fired up the sirens against a fast spreading infectious disease caused by a newly discovered Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and gave this disease the name COVID-19. While there is currently no specific treatment for COVID-19, several off label drugs approved for other indications are being investigated in clinical trials across the globe. In the last decade, theranostic nanoparticles were reported as promising tool for efficiently and selectively deliver therapeutic moieties (i.e. drugs, vaccines, siRNA, peptide) to target sites of infection. In addition, they allow monitoring infectious sides and treatment responses using noninvasive imaging modalities. While intranasal delivery was proposed as the preferred administration route for therapeutic agents against viral pulmonary diseases, NP-based delivery systems offer numerous benefits to overcome challenges associated with mucosal administration, and ensure that these agents achieve a concentration that is many times higher than expected in the targeted sites of infection while limiting side effects on normal cells. In this article, we have shed light on the promising role of nanoparticles as effective carriers for therapeutics or immune modulators to help in fighting against COVID-19.

Cancer heterogeneity and drug resistance limit the efficacy of cancer therapy. To address this issue, we have developed an integrated treatment protocol for effective treatment of heterogeneous ovarian cancer. An amphiphilic polymer coated magnetic iron oxide nanoparticle was conjugated with near infrared dye labeled HER2 affibody and chemotherapy drug cisplatin. The effects of the theranostic nanoparticle on targeted drug delivery, therapeutic efficacy, non-invasive magnetic resonance image (MRI)-guided therapy, and optical imaging detection of therapy resistant tumors were examined in an orthotopic human ovarian cancer xenograft model with highly heterogeneous levels of HER2 expression. We found that systemic delivery of HER2-targeted magnetic iron oxide nanoparticles carrying cisplatin significantly inhibited the growth of primary tumor and peritoneal and lung metastases in the ovarian cancer xenograft model in nude mice. Differential delivery of theranostic nanoparticles into individual tumors with heterogeneous levels of HER2 expression and various responses to therapy were detectable by MRI. We further found a stronger therapeutic response in metastatic tumors compared to primary tumors, likely due to a higher level of HER2 expression and a larger number of proliferating cells in metastatic tumor cells. Relatively long-time retention of iron oxide nanoparticles in tumor tissues allowed interrogating the relationship between nanoparticle drug delivery and the presence of resistant residual tumors by molecular imaging and histological analysis of the tumor tissues. Following therapy, most of the remaining tumors were small, primary tumors that had low levels of HER2 expression and nanoparticle drug accumulation, thereby explaining their lack of therapeutic response. However, a few residual tumors had HER2-expressing tumor cells and detectable nanoparticle drug delivery but failed to respond, suggesting additional intrinsic resistant mechanisms. Nanoparticle retention in the small residual tumors, nevertheless, produced optical signals for detection by spectroscopic imaging. The inability to completely excise peritoneal metastatic tumors by debulking surgery as well as resistance to chemotherapy are the major clinical challenges for ovarian cancer treatment. This targeted cancer therapy has the potential for the development of effective treatment for metastatic ovarian cancer.

Any variation in normal cellular function results in mitochondrial dysregulation that occurs in several diseases, including cancer. Such processes as oxidative stress, metabolism, signaling, and biogenesis play significant roles in cancer initiation and progression. Due to their central role in cellular metabolism, mitochondria are favorable therapeutic targets for the prevention and treatment of conditions like neurodegenerative diseases, diabetes, and cancer. Subcellular mitochondria-specific theranostic nanoformulations for simultaneous targeting, drug delivery, and imaging of these organelles are of immense interest in cancer therapy. It is a challenging task to cross multiple barriers to target mitochondria in diseased cells. To overcome these multiple barriers, several mitochondriotropic nanoformulations have been engineered for the transportation of mitochondria-specific drugs. These nanoformulations include liposomes, dendrimers, carbon nanotubes, polymeric nanoparticles (NPs), and inorganic NPs. These nanoformulations are made mitochondriotropic by conjugating them with moieties like dequalinium, Mito-Porter, triphenylphosphonium, and Mitochondria-penetrating peptides. Most of these nanoformulations are meticulously tailored to control their size, charge, shape, mitochondriotropic drug loading, and specific cell-membrane interactions. Recently, some novel mitochondria-selective antitumor compounds known as mitocans have shown high toxicity against cancer cells. These selective compounds form vicious oxidative stress and reactive oxygen species cycles within cancer cells and ultimately push them to cell death. Nanoformulations approved by the FDA and EMA for clinical applications in cancer patients include Doxil, NK105, and Abraxane. The novel use of these NPs still faces tremendous challenges and an immense amount of research is needed to understand the proper mechanisms of cancer progression and control by these NPs. Here in this review, we summarize current advancements and novel strategies of delivering different anticancer therapeutic agents to mitochondria with the help of various nanoformulations.

The tumor microenvironment (TME) is a dynamic and heterogeneous ecosystem whose abnormal vasculature, dense extracellular matrix, metabolic reprogramming and immunosuppression collectively hinder drug penetration, drive therapeutic resistance and limit responses to immunotherapy. TME-responsive nanomedicine provides an emerging toolbox to both monitor and actively remodel the microenvironment for precision cancer therapy. In this narrative review, we first summarize key pathological features of the TME and their impact on drug delivery across classical barriers, including the blood-brain, cutaneous and ocular interfaces, as well as circulating and bone-marrow niches in hematologic malignancies. We then discuss design principles of endogenous and exogenous stimuli-responsive nanoplatforms, and how these systems enable TME monitoring via liquid biopsy, spatial multi-omics and real-time imaging, and TME modulation through metabolic reprogramming, immune activation, vascular normalization and extracellular-matrix remodeling. Finally, we highlight major translational challenges and future opportunities, emphasizing the roles of artificial intelligence, multiscale and quantum-inspired modeling, and closed-loop theranostic strategies in optimizing TME-responsive nanomedicines for clinically meaningful benefit.

Theranostic nanoparticles are integrated systems useful for simultaneous diagnosis and imaging guided delivery of therapeutic drugs, with wide ranging potential applications in the clinic. Here we developed a theranostic nanoparticle (~ 24 nm size by dynamic light scattering) p-FE-PTX-FA based on polymeric micelle encapsulating an organic dye (FE) fluorescing in the 1,000–1,700 nm second near-infrared (NIR-II) window and an anti-cancer drug paclitaxel. Folic acid (FA) was conjugated to the nanoparticles to afford specific binding to molecular folate receptors on murine breast cancer 4T1 tumor cells. In vivo , the nanoparticles accumulated in 4T1 tumor through both passive and active targeting effect. Under an 808 nm laser excitation, fluorescence detection above 1,300 nm afforded a large Stokes shift, allowing targeted molecular imaging tumor with high signal to background ratios, reaching a high tumor to normal tissue signal ratio (T/NT) of (20.0 ± 2.3). Further, 4T1 tumors on mice were completed eradicated by paclitaxel released from p-FE-PTA-FA within 20 days of the first injection. Pharmacokinetics and histology studies indicated p-FE-PTX-FA had no obvious toxic side effects to major organs. This represented the first NIR-II theranostic agent developed.

Introduction:Gold nanoparticles (AuNPs) have unique properties that promise new and improved methods for targeting cancer treatment and diagnosis. However, despite their relatively high biocompatibility, AuNPs can negatively affect cell viability. Research indicates that the interactions with the plasma membrane and cellular uptake of AuNPs depend significantly on size, shape, and surface modifications.Material and methods:We evaluated the use of human lymphocyte primary culture as a model for assessing the to­xicity of AuNPs in proliferating cells. We compared the toxicity of rod-shaped, PEGylated AuNPs (gold nanorods, AuNRs) of two different sizes and gold nanospheres (AuNSs).Results:Our results show that at high concentrations, both AuNSs and AuNRs negatively affect the viability of activated human lymphocytes in vitro. The cytotoxic effect varies with size and concentration, with larger AuNRs (approx. 22 × 50 nm) being more toxic than smaller ones (approx. 20 × 40 nm) and 15 nm AuNSs exhibiting the lowest toxicity.Conclusions:Our results confirm that the application of AuNPs in cancer the­rapy and diagnostics must be accompanied by a thorough cytotoxicity assessment. Despite certain limitations, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction test for viability assessment of proliferating cells proves to be a simple and cost-effective method useful in nanoparticle toxicity studies.

Ovarian cancer continues to be the most lethal gynaecological malignancy, principally due to its late-stage diagnosis, extensive peritoneal dissemination, chemoresistance, and limitations of current imaging and therapeutic strategies. By optimising pharmacokinetics, refining tumour-selective drug delivery, and supporting high-resolution, multimodal imaging, nanomedicine offers a versatile platform to address these limitations. In this review, current progress across lipid-based, polymeric, inorganic, hybrid, and biomimetic nanocarriers is synthesised, emphasising how tailored physiochemical properties, surface functionalisation, and stimuli-responsive designs can improve tumour localisation, surmount stromal and ascetic barriers, and enable controlled drug release. Concurrently, significant advancement in imaging nanoprobes, including magnetic resonance imaging (MRI), positron emission tomography (PET)/single-photon emission computed tomography (SPECT), optical, near-infrared imaging (NIR), ultrasound, and photoacoustic systems, has evolved early lesion detection, intraoperative guidance, and quantitative monitoring of treatment. Diagnosis and therapy are further integrated within single platforms by emerging theranostic constructs, encouraging real-time visualisation of drug distribution and treatment response. Additionally, immune-nanomedicine, intraperitoneal depot systems, and nucleic acid-centred nanotherapies offer promising strategies to address immune suppression and molecular resistance in advanced ovarian cancer. In spite of noteworthy achievements, clinical translation is limited by complex manufacturing requirements, challenges with safety and stability, and restricted patient stratification. To unlock the full clinical potential of nanotechnology in ovarian cancer management, constant innovation in scalable design, regulatory standardisation, and integration of precision biomarkers will be necessary.

Background Prostate cancer (PCa) is a major cause of cancer‐associated death in men. A crucial factor in its development and treatment resistance is tumor hypoxia, which drives metabolic reprogramming (especially reconfiguration towards glycolysis), mediated to a great extent by hypoxia‐inducible factor‐“HIF‐1 alpha” (HIF‐1a). Aims The present review summarizes (i) the mechanisms underlying hypoxia‐induced glycolysis that enhances the aggressiveness of and treatment failure in PCa and (ii) recent developments in the field of theranostic nanoparticles (TNPs) with dual actions of inhibiting HIF‐1a and downstream metabolic targets, while facilitating the imaging and treatment of the tumor. Materials and Methods We summarize available evidence for the hypoxia‐glycolysis signaling in PCa and assess nanotechnology achievable theranostic approaches (i.e., liposomal‐, polymer‐ and metallic nanoplatforms) to promote drug delivery, real‐time tumor picture and modulation of hypoxic tumor microenvironments. Results Hypoxia‐inducible factor‐1 alpha (HIF‐1a) driven hypoxia is a common phenotypic feature that underlies the increased glycolysis and aggressive tumor phenotype. TNPs have been developed with the aim of (a) enhancing the drug bioavailability, (b) enabling the selectivity of tumor and imaging, and (c) reducing the hypoxia‐linked metabolic pathways. The use of PCa as a model for TNP development is especially timely as hypoxia crosses the intersection of androgen receptor (AR) signaling heavens (hormone therapy resistance) leading to progression to castration‐resistant PCa (CRPC) and as the Prostate‐Specific Membrane Antigen (PSMA) is greatly overexpressed and is a validated target for custom imaging and treatment. Discussion Compared with other hypoxia mediated solid tumors, hypoxia AR axis and PSMA overexpression have unique biological leverage for precision theranostics in PCa. Nevertheless, translation is limited by the issues of biocompatibility, complexities resulting from systematic regulations and constraints of scale‐up manufacturing. Conclusion TNPs are a promising platform to integrate diagnosis and treatment of PCa as they incorporate features of targeted delivery, on‐line monitoring and interference with HIF‐1a regulated glycolysis. Future advances will require interdisciplinary optimization, development of better tumor‐targeting approaches, and artificial intelligence guided nanoparticle design to facilitate clinical scale up and regulation of technically and clinically acceptable theranostics of nanomedicines for PCa. The debate in the field of cancer immunotherapy is being changed as nanotechnology breaks the obstacle of cancer immune evasion, target delivery, and systemic toxicity. Esthetically advanced methods that are discussed in this review are nanovaccine, nanoparticle‐enabled checkpoint barrier, cytokine delivery, and T‐cell modulation techniques that augment immune activation and increase tumor selectivity. It also presents the current clinical progress and approved nano‐immunotherapeutics and highlights their safety and translatability. Collectively, these technologies place nanotechnology as an important determinant of the next‐generation, personalized cancer immunotherapy.

β-cyclodextrin(βCD)-based star polymers have attracted much interest because of their unique structures and potential biomedical and biological applications. Herein, a well-defined folic acid (FA)-conjugated and disulfide bond-linked star polymer ((FA-Dex-SS)-βCD-(PCL)14) was synthesized via a couple reaction between βCD-based 14 arms poly(ε-caprolactone) (βCD-(PCL)14) and disulfide-containing α-alkyne dextran (alkyne-SS-Dex), and acted as theranostic nanoparticles for tumor-targeted MRI and chemotherapy. Theranostic nanoparticles were obtained by loading doxorubicin (DOX), and superparamagnetic iron oxide (SPIO) particles were loaded into the star polymer nanoparticles to obtain ((FA-Dex-SS)-βCD-(PCL)14@DOX-SPIO) theranostic nanoparticles. In vitro drug release studies showed that approximately 100% of the DOX was released from disulfide bond-linked theranostic nanoparticles within 24 h under a reducing environment in the presence of 10.0 mM GSH. DOX and SPIO could be delivered into HepG2 cells efficiently, owing to the folate receptor-mediated endocytosis process of the nanoparticles and glutathione (GSH), which triggered disulfide-bonds cleaving. Moreover, (FA-Dex-SS)-βCD-(PCL)14@DOX-SPIO showed strong MRI contrast enhancement properties. In conclusion, folic acid-decorated reduction-sensitive star polymeric nanoparticles are a potential theranostic nanoparticle candidate for tumor-targeted MRI and chemotherapy.