Ultimate fate, transformation, and toxicological consequences of herbicide pretilachlor to biotic components and associated environment: An overview.

Herbicides are applied for effective weed management in order to increase the crop yield. In recent decades, the overuse of these chemicals has posed adverse effects on different biotic components of the environment. Pretilachlor has been widely used during last few decades for weed management in paddy crop. Its excessive use may prove fatal for environment, various organisms, and nontarget plants. Thus, it is pertinent to know the extent to which herbicide residues remain in environment. The potential mobility and the release rate of herbicide in the soil are important factors governing ecotoxicological impact and degradation rate. Therefore, several techniques are being investigated for its effective removal from the contaminated sites. Furthermore, efforts have also been made to study the degradation of pretilachlor by various physicochemical processes, resulting into the formation of different types of metabolites. This review summarizes the available information on environmental fate, various degradation processes, microbial biotransformation, metabolites formed, ecotoxicological effects, techniques for detection in environmental samples, effect of safener, and various control release formulations for sustained release of pretilachlor in applied fields. The information so obtained will be very advantageous in deciding the future policies for safe and judicious use of the herbicide by maintaining health and environmental sustainability.

Nanophytomedicine: A promising practical approach in phytotherapy.

The long and rich history of herbal therapeutic nutrients is fascinating. It is incredible to think about how ancient civilizations used plants and herbs to treat various ailments and diseases. One group of bioactive phytochemicals that has gained significant attention recently is dietary polyphenols. These compounds are commonly found in a variety of fruits, vegetables, spices, nuts, drinks, legumes, and grains. Despite their incredible therapeutic properties, one challenge with polyphenols is their poor water solubility, stability, and bioavailability. This means that they are not easily absorbed by the body when consumed in essential diets. Because of structural complexity, polyphenols with high molecular weight cannot be absorbed in the small intestine and after arriving in the colon, they are metabolized by gut microbiota. However, researchers are constantly working on finding solutions to enhance the bioavailability and absorption of these compounds. This study aims to address this issue by applying nanotechnology approaches to overcome the challenges of the therapeutic application of dietary polyphenols. This combination of nanotechnology and phytochemicals could cause a completely new field called nanophytomedicine or herbal nanomedicine.

Berberine and berberine nanoformulations in cancer therapy: Focusing on lung cancer.

Lung cancer is the second most prevalent cancer and ranks first in cancer-related death worldwide. Due to the resistance development to conventional cancer therapy strategies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, various natural products and their extracts have been revealed as alternatives. Berberine (BBR), which is present in the stem, root, and bark of various trees, could exert anticancer activities by regulating tumor cell proliferation, apoptosis, autophagy, metastasis, angiogenesis, and immune responses via modulating several signaling pathways within the tumor microenvironment. Due to its poor water solubility, poor pharmacokinetics/bioavailability profile, and extensive p-glycoprotein-dependent efflux, BBR application in (pre) clinical studies is restricted. To overcome these limitations, BBR can be encapsulated in nanoparticle (NP)-based drug delivery systems, as monotherapy or combinational therapy, and improve BBR therapeutic efficacy. Nanoformulations also facilitate the selective delivery of BBR into lung cancer cells. In addition to the anticancer activities of BBR, especially in lung cancer, here we reviewed the BBR nanoformulations, including polymeric NPs, metal-based NPs, carbon nanostructures, and others, in the treatment of lung cancer.

Curcumin - Bioavailability Enhancement by Prodrug Approach and Novel Formulations.

Curcumin is a diverse natural pharmacological agent involved in various signal transduction mechanisms. Therapeutically, this potent molecule faces different challenges and issues related to low bioavailability due to its poor aqueous solubility, less permeability, faster elimination and clearance. Experts in synthetic chemistry and pharmaceuticals are continuously sparing their efforts to overcome these pharmacokinetic challenges by using different structural modification strategies and developing novel drug delivery systems. In this mini-review article, we are focusing on development of curcumin derivatives by different possible routes like conjugation with biomolecules, natural polymers, synthetic polymers, natural products, metal conjugates and co- administration with natural metabolic inhibitors. In addition to that, it was also focused on the preparation of modified formulations such as micelles, microemulsions, liposomes, complexes with phospholipids, micro and nanoemulsions, solid lipid nanoparticles, nano lipid carriers, biopolymer nanoparticles and microgels to improve the pharmacokinetic properties of the curcumin without altering its pharmacodynamics activity. This review helps to understand the problems associated with curcumin and different strategies to improve its pharmacokinetic profile.

Skin Protection by Carotenoid Pigments.

Sunlight, despite its benefits, can pose a threat to the skin, which is a natural protective barrier. Phototoxicity caused by overexposure, especially to ultraviolet radiation (UVR), results in burns, accelerates photoaging, and causes skin cancer formation. Natural substances of plant origin, i.e., polyphenols, flavonoids, and photosynthetic pigments, can protect the skin against the effects of radiation, acting not only as photoprotectors like natural filters but as antioxidant and anti-inflammatory remedies, alleviating the effects of photodamage to the skin. Plant-based formulations are gaining popularity as an attractive alternative to synthetic filters. Over the past 20 years, a large number of studies have been published to assess the photoprotective effects of natural plant products, primarily through their antioxidant, antimutagenic, and anti-immunosuppressive activities. This review selects the most important data on skin photodamage and photoprotective efficacy of selected plant carotenoid representatives from in vivo studies on animal models and humans, as well as in vitro experiments performed on fibroblast and keratinocyte cell lines. Recent research on carotenoids associated with lipid nanoparticles, nanoemulsions, liposomes, and micelles is reviewed. The focus was on collecting those nanomaterials that serve to improve the bioavailability and stability of carotenoids as natural antioxidants with photoprotective activity.

New Avenues and Major Achievements in Phytocompounds Research for Glioblastoma Therapy.

Phytocompounds have been evaluated for their anti-glioblastoma actions for decades, with promising results from preclinical studies but only limited translation into clinics. Indeed, by targeting multiple signaling pathways deregulated in cancer, they often show high efficacy in the in vitro studies, but their poor bioavailability, low tumor accumulation, and rapid clearance compromise their efficacy in vivo. Here, we present the new avenues in phytocompound research for the improvement of glioblastoma therapy, including the ways to enhance the response to temozolomide using phytochemicals, the current focus on phytocompound-based immunotherapy, or the use of phytocompounds as photosensitizers in photodynamic therapy. Moreover, we present new, intensively evaluated approaches, such as chemical modifications of phytochemicals or encapsulation into numerous types of nanoformulations, to improve their bioavailability and delivery to the brain. Finally, we present the clinical trials evaluating the role of phytocompounds or phytocompound-derived drugs in glioblastoma therapy and the less studied phytocompounds or plant extracts that have only recently been found to possess promising anti-glioblastoma properties. Overall, recent advancements in phytocompound research are encouraging; however, only with more 3D glioblastoma models, in vivo studies, and clinical trials it is possible to upgrade the role of phytocompounds in glioblastoma treatment to a satisfactory level.

The Promising Role of Polyphenols in Skin Disorders.

The biochemical characteristics of polyphenols contribute to their numerous advantageous impacts on human health. The existing research suggests that plant phenolics, whether consumed orally or applied directly to the skin, can be beneficial in alleviating symptoms and avoiding the development of many skin disorders. Phenolic compounds, which are both harmless and naturally present, exhibit significant potential in terms of counteracting the effects of skin damage, aging, diseases, wounds, and burns. Moreover, polyphenols play a preventive role and possess the ability to delay the progression of several skin disorders, ranging from small and discomforting to severe and potentially life-threatening ones. This article provides a concise overview of recent research on the potential therapeutic application of polyphenols for skin conditions. It specifically highlights studies that have investigated clinical trials and the use of polyphenol-based nanoformulations for the treatment of different skin ailments.

Phospholipid Complex Formulation Technology for Improved Drug Delivery in Oncological Settings: a Comprehensive Review.

Addressing poor solubility and permeability issues associated with synthetic drugs and naturally occurring active compounds is crucial for improving bioavailability. This review explores the potential of phospholipid complex formulation technology to overcome these challenges. Phospholipids, as endogenous molecules, offer a viable solution, with drugs complexed with phospholipids demonstrating a similar absorption mechanism. The non-toxic and biodegradable nature of the phospholipid complex positions it as an ideal candidate for drug delivery. This article provides a comprehensive exploration of the mechanisms underlying phospholipid complexes. Special emphasis is placed on the solvent evaporation method, with meticulous scrutiny of formulation aspects such as the phospholipid ratio to the drug and solvent. Characterization techniques are employed to understand structural and functional attributes. Highlighting the adaptability of the phospholipid complex, the review discusses the loading of various nanoformulations and emulsion systems. These strategies aim to enhance drug delivery and efficacy in various malignancies, including breast, liver, lung, cervical, and pancreatic cancers. The broader application of the drug phospholipid complex is showcased, emphasizing its adaptability in diverse oncological settings. The review not only explores the mechanisms and formulation aspects of phospholipid complexes but also provides an overview of key clinical studies and patents. These insights contribute to the intellectual and translational advancements in drug phospholipid complexes.

An Easily Accessible NIR-Absorbing Tetraimide Dye and its Biotherapeutics Based Photothermal and Photodynamic Therapy.

Organic π-systems with strong absorption in the near-infrared (NIR) region are promising candidates for photothermal therapy (PTT) and photodynamic therapy (PDT). However, the synthesis of NIR π-systems involves several steps and many of them display poor photothermal conversion efficiency (PTCE). Here we present the synthesis of a tetraimide-based donor-acceptor NIR π-system, 2EHex-B having absorbance in the range of 350-900 nm. Importantly, 2EHex-B is synthesized in two steps with a 70 % high yield. Moreover, 2EHex-B shows excellent PTCE up to 50 % and good biocompatibility when encapsulated in liposomes. The liposome coated 2EHex-B, (L-2EHex-B) showed good thermal stability and efficiently kills cancer cells via PTT. Additionally, L-2EHex-B shows good reactive singlet oxygen generation ability when irradiated with a 750 nm laser. 3D cell culture model - multicellular spheroids test was performed to evaluate the efficiency of PTT. The spheroids treated with L-2EHex-B after NIR light irradiation showed increased cell death from the core of the tumor toward the periphery. The easy access to 2EHex-B makes it a potential candidate for minimally invasive cancer treatment.

Multiple potential strategies for the application of nisin and derivatives.

Nisin is a naturally occurring bioactive small peptide produced by Lactococcus lactis subsp. lactis and belongs to the Type A (I) lantibiotics. Due to its potent antimicrobial activity, it has been broadly employed to preserve various food materials as well as to combat a variety of microbial pathogens. The present review discusses the antimicrobial properties of nisin and different types of their derivatives employed to treat microbial pathogens with a detailed underlying mechanism of action. Several alternative strategies such as combination, conjugation, and nanoformulations have been discussed in order to address several issues such as rapid degradation, instability, and reduced activity due to the various environmental factors that arise in the applications of nisin. Furthermore, the evolutionary relationship of many nisin genes from different nisin-producing bacterial species has been investigated. A detailed description of the natural and bioengineered nisin variants, as well as the underlying action mechanisms, has also been provided. The chemistry used to apply nisin in conjugation with natural or synthetic compounds as a synergetic mode of antimicrobial action has also been thoroughly discussed. The current review will be useful in learning about recent and past research that has been performed on nisin and its derivatives as antimicrobial agents.

Compendium of naringenin: potential sources, analytical aspects, chemistry, nutraceutical potentials and pharmacological profile.

Naringenin is flavorless, water insoluble active principle belonging to flavanone subclass. It exhibits a diverse pharmacological profile as well as divine nutraceutical values. Although several researchers have explored this phytoconstituent to evaluate its promising properties, still it has not gained recognition at therapeutic levels and more clinical investigations are still required. Also the neutraceutical potential has limited marketed formulations. This compilation includes the description of reported therapeutic potentials of naringenin in variety of pathological conditions alongwith the underlying mechanisms. Details of various analytical investigations carried on this molecule have been provided along with brief description of chemistry and structural activity relationship. In the end, various patents filed and clinical trial data has been provided. Naringenin has revealed promising pharmacological activities including cardiovascular diseases, neuroprotection, anti-diabetic, anticancer, antimicrobial, antiviral, antioxidant, anti-inflammatory and anti-platelet activity. It has been marketed in the form of nanoformulations, co-crystals, solid dispersions, tablets, capsules and inclusion complexes. It is also available in various herbal formulations as nutraceutical supplement. There are some pharmacokinetic issue with naringenin like poor absorption and low dissolution rate. Although these issues have been sorted out upto certain extent still further research to investigate the bioavailability of naringenin from herbal supplements and its clinical efficacy is essential.

A comprehensive compiled review is presented on source, health benefits, chemistry and analysis, and marketed products of naringenin.Naringenin is a promising phytoconstituent as nutraceutical.Valorization of fruit peels of citrus fruits is a critical step for food and nutraceutical industry.Structure-activity relationship of naringenin derivatives.Nano-formulations incorporating naringenin in themselves can be used for targeted delivery for critical disorders.Naringenin obtained from the peels can be efficiently used in breads, cookies, cakes and other food products.

Nanotechnological interventions in bacteriocin formulations - advances, and scope for challenging food spoilage bacteria and drug-resistant foodborne pathogens.

Food spoilage bacteria (FSB) and multidrug-resistant (MDR) foodborne pathogens have emerged as one of the principal public health concerns in the twenty first century. The harmful effects of FSB lead to economic losses for the food industries. Similarly, MDR foodborne pathogens are accountable for multiple illnesses and pose a threat to consumers. Therefore, there is an urgent need to establish effective formulations for successful application against such microorganisms. In this context, the fusion of knowledge from biotechnology and nanotechnology can explore endless possibilities in the development of innovative formulations against FSB and foodborne pathogens. The current review critically examines the application of bacteriocins in the food industry and the use of nanomaterials to enhance the antimicrobial activity, stability, and precision in the target delivery of bacteriocins. This review also explores the technologies involved in the development of bacteriocin-based nanoformulations and their action against FSB and MDR foodborne pathogens, offering new possibilities in preservation technologies and addressing food safety issues in the food industry. The review highlights the challenges in the commercialization and technoeconomical feasibility of nanobacteriocin. Overall, it provides essential information and interpretation about nanotechnological advancements in bacteriocin formulation action against FSB and foodborne pathogens and future scopes.

Regenerative marine waste towards CaCO3 nanoformulation for Alzheimer's therapy.

Alzheimer's disorder (AD) is associated with behavioural and cognitive destruction with due respect to the neurological degeneration. Conventional therapeutic approach for treatment of AD using neuroprotective drugs suffered certain limitations such as poor solubility, insufficient bioavailability, adverse side effects at higher dose and ineffective permeability on blood brain barrier (BBB). Development of nanomaterial based drug delivery system helped to overcome these barriers. Hence the present work focused on encapsulating neuroprotective drug citronellyl acetate within CaCO3 nanoparticles to develop neuroprotective CaCO3 nanoformulation (CA@CaCO3 NFs). CaCO3 was derived from marine conch shell waste, while the neuroprotective drug citronellyl acetate was scrutinized by in-silico high throughput screening. In-vitro findings revealed that CA@CaCO3 nanoformulation exhibited enhanced free radical scavenging activity of 92% (IC50 value - 29.27 ± 2.6 µg/ml), AChE inhibition of 95% (IC50 value - 25.6292 ± 1.5 µg/ml) at its maximum dose (100 µg/ml). CA@CaCO3 NFs attenuated the aggregation of ß-amyloid peptide (Aß) and also disaggregated the preformed mature plaques the major risk factor for AD. Overall, the present study reveals that CaCO3 nanoformulations exhibits potent neuroprotective potential when compared to the CaCO3 nanoparticles alone and citronellyl acetate alone due to the sustained drug release and synergistic effect of CaCO3 nanoparticles and citronellyl acetate depicting the fact that CaCO3 can act as promising drug delivery system for treatment of neurodegenerative and CNS related disorders.

Curcumin in the treatment of liver cancer: From mechanisms of action to nanoformulations.

Liver cancer is the sixth most prevalent cancer and ranks third in cancer-related death, after lung and colorectal cancer. Various natural products have been discovered as alternatives to conventional cancer therapy strategies, including radiotherapy, chemotherapy, and surgery. Curcumin (CUR) with antiinflammatory, antioxidant, and antitumor activities has been associated with therapeutic benefits against various cancers. It can regulate multiple signaling pathways, such as PI3K/Akt, Wnt/ß-catenin, JAK/STAT, p53, MAPKs, and NF-ĸB, which are involved in cancer cell proliferation, metastasis, apoptosis, angiogenesis, and autophagy. Due to its rapid metabolism, poor oral bioavailability, and low solubility in water, CUR application in clinical practices is restricted. To overcome these limitations, nanotechnology-based delivery systems have been applied to use CUR nanoformulations with added benefits, such as reducing toxicity, improving cellular uptake, and targeting tumor sites. Besides the anticancer activities of CUR in combating various cancers, especially liver cancer, here we focused on the CUR nanoformulations, such as micelles, liposomes, polymeric, metal, and solid lipid nanoparticles, and others, in the treatment of liver cancer.

Nanoformulations as a strategy to overcome the delivery limitations of cannabinoids.

Medical cannabis has received significant interest in recent years due to its promising benefits in the management of pain, anxiety, depression and neurological and movement disorders. Specifically, the major phytocannabinoids derived from the cannabis plant such as (-) trans-Δ9 -tetrahydrocannabinol (THC) and cannabidiol (CBD), have been shown to be responsible for the pharmacological and therapeutic properties. Recently, these phytocannabinoids have also attracted special attention in cancer treatment due to their well-known palliative benefits in chemotherapy-induced nausea, vomiting, pain and loss of appetite along with their anticancer activities. Despite the enormous pharmacological benefits, the low aqueous solubility, high instability (susceptibility to extensive first pass metabolism) and poor systemic bioavailability restrict their utilization at clinical perspective. Therefore, drug delivery strategies based on nanotechnology are emerging to improve pharmacokinetic profile and bioavailability of cannabinoids as well as enhance their targeted delivery. Here, we critically review the nano-formulation systems engineered for overcoming the delivery limitations of native phytocannabinoids including polymeric and lipid-based nanoparticles (lipid nano capsules (LNCs), nanostructured lipid carriers (NLCs), nanoemulsions (NE) and self-emulsifying drug delivery systems (SEDDS)), ethosomes and cyclodextrins as well as their therapeutic applications.

Nanotechnology Formulations Designed with Herbal Extracts and Their Therapeutic Applications - A Review.

Because of the increasing demand for natural products, the development of nanoformulations containing natural active ingredients requires in-depth knowledge of the substances used, methods of obtaining, and stability profiles to ensure product quality, efficacy, and safety. Considering this, the bibliography of the last five years presented in databases (PubMed and Science Direct) was discussed in this work, discussing the study with medicinal plants to obtain active metabolites with therapeutic properties, as well as the different nano-systems responsible for carrying these molecules. Due to the wealth of biodiversity found in the world, many species are submitted to the extraction process for several purposes. However, identifying, classifying, and quantifying the constituents of herbal matrices are crucial steps to verify their therapeutic potential. In addition, knowing the techniques of production and elaboration of nanotechnology products allows the optimization of the incorporation of herbal extracts as an innovation target. For studies to be successful, it is necessary to exhaust experimental results that guarantee the efficacy, safety, and quality of natural nanosystems, with the objective of obtaining reliable answers in nanotechnology therapy.

Enhancement of suppression oxidative stress and inflammation of quercetin by nano-decoration for ameliorating silica-induced pulmonary fibrosis.

Silicosis is a life-threatening lung fibrotic disease caused by excessive inhalation of environmental exposure to crystalline silica-containing dust, whereas achieving therapeutic cures are constrained. Antioxidation and anti-inflammation are currently recognized as effective strategies to counteract organ fibrosis. Using naturally occurring phytomedicines quercetin (Qu) has emerged in antagonizing fibrotic disorders involving oxidative stress and inflammation, but unfortunately the hydrophilicity deficiency. Herein, chitosan-assisted encapsulation of Qu in nanoparticles (Qu/CS-NPs) was first fabricated for silicosis-associated fibrosis treatment by pulmonary delivery. Qu/CS-NPs with spherical diameters of ~160 nm, demonstrated a high Qu encapsulated capability, excellent hydrophilic stability, fantastic oxidation radical scavenging action, and outstanding controlled as well as slow release Qu action. A silicosis rat model induced by intratracheal instillation silica was established to estimate the anti-fibrosis effect of Qu/CS-NPs. After intratracheal administration, CS-NPs markedly enhanced Qu anti-fibrotic therapy efficacy, accompanying the evident changes in reducing ROS and MDA production to mitigate oxidative stress, inhibiting IL-1ß and TNF-α release, improving lung histological architecture, down-regulating α-SAM levels and suppressing ECM deposition, and thereby ameliorating silica-induced pulmonary fibrosis. Results manifested that the augmented antioxidant and anti-inflammatory activities of Qu by CS-NPs delivery was a result of achieving this remarkable improvement in curative effects. Combined with negligible systemic toxicity, nano-decorated Qu may provide a feasible therapeutic option for silicosis therapy.

A liposomal radionanoformulation for targeted drug delivery and real time monitoring by radionuclide imaging for HER2 overexpressing cancers.

Liposomal formulations carrying chemotherapeutic drugs have demonstrated great potential as effective drug delivery systems. Smart nanoformulations decorated with targeting agents and probes are desired for site specific delivery of drugs and real time monitoring. In this study, we aimed to develop liposomal formulation loaded with doxorubicin and tagged with trastuzumab antibody (Ab) for targeting human epidermal growth factor receptor 2 (HER2) positive tumors. Liposomes were prepared by ethanol injection method using modified lipids to conjugate trastuzumab and radiolabel with Tc-99m radioisotope using DTPA for imaging by single photon emission computed tomography (SPECT). Doxorubicin was loaded using the active pH gradient method. The conjugation of Ab to liposomes was validated by SDS-PAGE and MALDI-MS. 99m Tc labeled liposomes encapsulating doxorubicin conjugated with antibody (99m Tc-Lip-Ab-Dox) and 99m Tc labeled liposomes encapsulating doxorubicin (99m Tc-Lip-Dox) were found to be stable in blood plasma and saline using chromatography method. The specificity of 99m Tc-Lip-Ab-Dox against HER2 receptor was evident from cell uptake and inhibition studies. Results also corroborated with confocal microscopy studies. In vivo studies in tumor bearing severe combined immunodeficient mice by SPECT imaging and biodistribution studies revealed higher uptake of 99m Tc-Lip-Ab-Dox in tumor and less accumulation in the liver compared to 99m Tc-Lip-Dox. In conclusion, liposomal nanoformulation for immunotargeting and monitoring of drug delivery was successfully formulated and evaluated. Encouraging results in preclinical studies were obtained with the radioformulation. Such smart radioformulations will not only serve the purpose of site-specific controlled release of drugs at the target site but also aid in optimizing the drug doses and schedule of cancer treatment by monitoring pharmacokinetics.

The Role of Biological Rhythms in New Drug Formulations to Cross the Brain Barriers.

For brain protection, the blood-brain barrier and blood-cerebrospinal fluid barrier limit the traffic of molecules between blood and brain tissue and between blood and cerebrospinal fluid, respectively. Besides their protective function, brain barriers also limit the passage of therapeutic drugs to the brain, which constitutes a great challenge for the development of therapeutic strategies for brain disorders. This problem has led to the emergence of novel strategies to treat neurological disorders, like the development of nanoformulations to deliver therapeutic agents to the brain. Recently, functional molecular clocks have been identified in the blood-brain barrier and in the blood-cerebrospinal fluid barrier. In fact, circadian rhythms in physiological functions related to drug disposition were also described in brain barriers. This opens the possibility for chronobiological approaches that aim to use time to improve drug efficacy and safety. The conjugation of nanoformulations with chronobiology for neurological disorders is still unexplored. Facing this, here, we reviewed the circadian rhythms in brain barriers, the nanoformulations studied to deliver drugs to the brain, and the nanoformulations with the potential to be conjugated with a chronobiological approach to therapeutic strategies for the brain.

Recent Advances in Genome-Editing Technology with CRISPR/Cas9 Variants and Stimuli-Responsive Targeting Approaches within Tumor Cells: A Future Perspective of Cancer Management.

The innovative advances in transforming clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) into different variants have taken the art of genome-editing specificity to new heights. Allosteric modulation of Cas9-targeting specificity by sgRNA sequence alterations and protospacer adjacent motif (PAM) modifications have been a good lesson to learn about specificity and activity scores in different Cas9 variants. Some of the high-fidelity Cas9 variants have been ranked as Sniper-Cas9, eSpCas9 (1.1), SpCas9-HF1, HypaCas9, xCas9, and evoCas9. However, the selection of an ideal Cas9 variant for a given target sequence remains a challenging task. A safe and efficient delivery system for the CRISPR/Cas9 complex at tumor target sites faces considerable challenges, and nanotechnology-based stimuli-responsive delivery approaches have significantly contributed to cancer management. Recent innovations in nanoformulation design, such as pH, glutathione (GSH), photo, thermal, and magnetic responsive systems, have modernized the art of CRISPR/Cas9 delivery approaches. These nanoformulations possess enhanced cellular internalization, endosomal membrane disruption/bypass, and controlled release. In this review, we aim to elaborate on different CRISPR/Cas9 variants and advances in stimuli-responsive nanoformulations for the specific delivery of this endonuclease system. Furthermore, the critical constraints of this endonuclease system on clinical translations towards the management of cancer and prospects are described.