Nanoparticle-based Drug Delivery Systems Research Articles

Nanoparticle-Based Drug Delivery Systems Enhance Treatment of Cognitive Defects.

Nanoparticle-based drug delivery presents a promising solution in enhancing therapies for neurological diseases, particularly cognitive impairment. These nanoparticles address challenges related to the physicochemical profiles of drugs that hinder their delivery to the central nervous system (CNS). Benefits include improved solubility due to particle size reduction, enhanced drug penetration across the blood-brain barrier (BBB), and sustained release mechanisms suitable for long-term therapy. Successful application of nanoparticle delivery systems requires careful consideration of their characteristics tailored for CNS delivery, encompassing particle size and distribution, surface charge and morphology, loading capacity, and drug release kinetics. Literature review reveals three main types of nanoparticles developed for cognitive function enhancement: polymeric nanoparticles, lipid-based nanoparticles, and metallic or inorganic nanoparticles. Each type and its production methods possess distinct advantages and limitations. Further modifications such as coating agents or ligand conjugation have been explored to enhance their brain cell uptake. Evidence supporting their development shows improved efficacy outcomes, evidenced by enhanced cognitive function assessments, modulation of pro-oxidant markers, and anti-inflammatory activities. Despite these advancements, clinical trials validating the efficacy of nanoparticle systems in treating cognitive defects are lacking. Therefore, these findings underscore the need for researchers to expedite clinical testing to provide robust evidence of the potential of nanoparticle-based drug delivery systems.

Nanoparticles based drug delivery system for cancer

A medication delivery system based on nanoparticles is seen to be promising for the treatment of neoplasia. It demonstrates increased efficacy by prolonging the half-lives of the drug and proteins, improving the solubility of lipophilic medicines, and allowing for the precise and controlled release of the medication into the affected area. The main benefit of medication delivery systems based on nanoparticles is the treatment of tumors. It was also mentioned that tumors can be treated through angiogenesis. Patients using traditional medication therapy for tumor surfers may experience negative side effects from the chemotherapy medicines' non-selective activity on healthy cells.

PREPRINT Machine Learning for the Sensitivity Analysis of a Model of the Cellular Uptake of Nanoparticles for the Treatment of Cancer.

Experimental studies on the cellular uptake of nanoparticles (NPs), useful for the investigation of NP-based drug delivery systems, are often difficult to interpret due to the large number of parameters that can contribute to the phenomenon. It is therefore of great interest to identify insignificant parameters to reduce the number of variables used for the design of experiments. In this work, a model of the wrapping of elliptical NPs by the cell membrane is used to compare the influence of the aspect ratio of the NP, the membrane tension, the NP-membrane adhesion, and its variation during the interaction with the NP on the equilibrium state of the wrapping process. Several surrogate models, such as Kriging, Polynomial Chaos Expansion (PCE), and artificial neural networks (ANN) have been built and compared to emulate the computationally expensive model. Only the ANN-based model outperformed the other approaches by providing much better predictivity metrics and could therefore be used to compute the sensitivity indices. Our results showed that the NP's aspect ratio, the initial NP-membrane adhesion, the membrane tension, and the delay for the increase of the NP-membrane adhesion after receptor dynamics are the main contributors to the cellular internalization of the NP, while the influence of other parameters is negligible.

Cytotoxicity and photothermal properties of graphene oxide conjugate with folic acid and a cytostatic agent of styryl thiazolopyrimidinium class

ABSTRAСT In recent years, the field of nanomedicine has garnered significant attention, particularly in the development of advanced drug delivery systems. Among the promising materials, highly oxidized graphene oxide (GO) has emerged as key components due to unique physicochemical properties and biocompatibility. These materials offer novel avenues for targeted drug delivery, enhancing therapeutic efficacy while minimizing side effects. This article explores the innovative design of nanoparticle-based drug delivery systems utilizing highly oxidized graphene oxide with folic acid in combination with thiazolopyrimidinium salt, highlighting their potential applications in medicine.

Development of a Bentonite Nanoparticle-Based Transdermal Drug Delivery System for Burn Wound Infection Prevention

Development of a Bentonite Nanoparticle-Based Transdermal Drug Delivery System for Burn Wound Infection Prevention

Status Quo in the Liposome-Based Therapeutic Strategies Against Glioblastoma: "Targeting the Tumor and Tumor Microenvironment".

Glioblastoma is the most aggressive and fatal brain cancer, characterized by a high growth rate, invasiveness, and treatment resistance. The presence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) poses a challenging task for chemotherapeutics, resulting in low efficacy, bioavailability, and increased dose-associated side effects. Despite the rigorous treatment strategies, including surgical resection, radiotherapy, and adjuvant chemotherapy with temozolomide, overall survival remains poor. The failure of current chemotherapeutics and other treatment regimens in glioblastoma necessitates the development of new drug delivery methodologies to precisely and efficiently target glioblastoma. Nanoparticle-based drug delivery systems offer a better therapeutic option in glioblastoma, considering their small size, ease of diffusion, and ability to cross the BBB. Liposomes are a specific category of nanoparticles made up of fatty acids. Furthermore, liposomes can be surface-modified to target a particular receptor and are nontoxic. This review discusses various methods of liposome modification for active/directed targeting and various liposome-based therapeutic approaches in the delivery of current chemotherapeutic drugs and nucleic acids in targeting the glioblastoma and tumor microenvironment.

Peptide-Conjugated Vascular Endothelial Extracellular Vesicles Encapsulating Vinorelbine for Lung Cancer Targeted Therapeutics.

Lung cancer is one of the major cancer types and poses challenges in its treatment, including lack of specificity and harm to healthy cells. Nanoparticle-based drug delivery systems (NDDSs) show promise in overcoming these challenges. While conventional NDDSs have drawbacks, such as immune response and capture by the reticuloendothelial system (RES), extracellular vesicles (EVs) present a potential solution. EVs, which are naturally released from cells, can evade the RES without surface modification and with minimal toxicity to healthy cells. This makes them a promising candidate for developing a lung-cancer-targeting drug delivery system. EVs isolated from vascular endothelial cells, such as human umbilical endothelial-cell-derived EVs (HUVEC-EVs), have shown anti-angiogenic activity in a lung cancer mouse model; therefore, in this study, HUVEC-EVs were chosen as a carrier for drug delivery. To achieve lung-cancer-specific targeting, HUVEC-EVs were engineered to be decorated with GE11 peptides (GE11-HUVEC-EVs) via a postinsertional technique to target the epidermal growth factor receptor (EGFR) that is overexpressed on the surface of lung cancer cells. The GE11-HUVEC-EVs were loaded with vinorelbine (GE11-HUVEC-EVs-Vin), and then characterized and evaluated in in vitro and in vivo lung cancer models. Further, we examined the binding affinity of ABCB1, encoding P-glycoprotein, which plays a crucial role in chemoresistance via the efflux of the drug. Our results indicate that GE11-HUVEC-EVs-Vin effectively showed tumoricidal effects against cell and mouse models of lung cancer.

Emerging Nanoparticle-Based Herbal Drug Delivery Systems for Colon Targeting Therapy

Abstract: Herbal medications hold a dominant position in the pharmaceutical sector due to their well-established therapeutic effects and extremely low negative effects. Besides, herbal remedies are easily available and highly economical. However, to circumvent the issue of poor bioavailability, the combinatorial strategy of incorporating herbal medicines and nano-technology is useful. The phytoconstituents molded in novel nanocarriers such as polymeric nanoparticles, polymeric micelles, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, gold nanoparticles, etc., have been extensively investigated as they are the most promising approach for colon-targeting drug delivery systems. Although plant-based medicines have been developed for decades, there is enormous research interest in the development of an effective plant-derived delivery system for the incorporation of phytocon-stituents into various nanomaterials to overcome potential challenges related to solubility, bioavailability, and stability issues. The encapsulation of phytoconstituents in a novel nanocarrier is a promising approach to improving the bioavailability, stability, and therapeutic efficacy of herbal medicines. The herbal nanomedicines are used as a promising tool for tar-geted delivery to the colon, with potentially effective outcomes for the treatment of colonic diseases, viz., ulcerative colitis, diverticulitis, Crohn's disease, shigellosis, constipation, co-lonic polyps, colon cancer, etc. This article presents a comprehensive survey of recent find-ings and patents by innovators working exclusively on nanoparticles for the delivery of phy-tomedicines for colon targeting.

Ultrafast continuous flow-dialysis for nanoparticle-based drug delivery systems via microfluidic-multiple buffer injector

Nanoparticle-based drug delivery systems (NP-DDS) have emerged as promising carriers for bioactive organic molecules due to their potential in enhancing therapeutic effects. However, traditional purification methods like batch dialysis and diafiltration can alter NP-DDS bio-physicochemical properties due to the lengthy process, prolonged coexistence with organic solvents, and external forces. To address this challenge, we developed an ultrafast flow-dialysis microfluidic module with dual channels separated by a membrane layer. The module leverages multiple buffer injectors (MBIs) to accelerate dialysis by injecting fresh buffer into multiple dialysis zones of bottom channel, refreshing the concentration gradients over the mixture sample in the upper channel to maximize mass transfer efficiency. Using this method for a dual drug-loaded liposome sample containing doxorubicin and curcumin, impurities (such as ethanol and un-trapped drugs) removal and buffer exchange were rapidly terminated within 15 min, continuously operating for ∼ 6 hrs with sequential membrane regeneration process. Importantly, unlike traditional methods, the MBI process maintains the initial uniformity in the size and distribution of liposomes with no leakage of the encapsulated drugs. In vitro HeLa cell tests reveal that the liposomes purified by MBI exhibited significantly higher cellular uptake (1.13 ∼ 1.67 fold), presumably due to the small and uniform size of liposomes, leading to improved anti-tumor effects. Notably, the MBI platform’s versatility was further verified by purifying a mixture of laccase enzyme and by removing the used organic solvents from various carriers (e.g., lipid-based, polymeric, and protein nanoparticles). It is envisioned that the outstanding performance of ultrafast dialysis will enables a continuous-flow downstream process for diverse nano-carriers by intensifying with extra steps in the manufacturing of nanomedicnes, including targeted drug delivery and cancer therapy.

Synthesis, Characterization and Targeted Drug Delivery of Curcumin-Loaded PLGA Nanoparticles

Background: Nanoparticle-based drug delivery systems have revolutionized therapeutic delivery, offering advantages such as enhanced bioavailability, controlled release, and targeted delivery to diseased tissues. Among these, polymeric nanoparticles, especially those utilizing poly(lactic-co-glycolic acid) (PLGA), have shown significant potential due to their biocompatibility, biodegradability, and stability. Curcumin, a polyphenolic compound with potent anti-inflammatory and anticancer properties, faces clinical limitations due to poor solubility and low bioavailability. Encapsulation in PLGA nanoparticles could enhance curcumin’s therapeutic efficacy by improving stability, controlled release, and targeted delivery. Methods: Curcumin-loaded PLGA nanoparticles were synthesized using a solvent evaporation method. Nanoparticles were characterized using dynamic light scattering (DLS) for size and zeta potential, and scanning electron microscopy (SEM) for morphology. In vitro drug release was assessed using a dialysis method, while cytotoxicity and anti-inflammatory activity were evaluated using MTT and nitric oxide inhibition assays, respectively. Results: DLS analysis revealed an average particle size of 150 ± 10 nm and a zeta potential of -25 ± 2 mV, indicating stability and suitability for therapeutic applications. SEM imaging showed smooth, spherical nanoparticles. Drug release studies displayed a biphasic pattern, with an initial burst followed by sustained release over 72 hours. Cytotoxicity assays demonstrated enhanced anticancer activity of curcumin-loaded nanoparticles compared to free curcumin, with a significantly lower IC50 value (5 ± 0.5 µM versus 15 ± 1.0 µM). Anti-inflammatory studies showed a 60% inhibition of nitric oxide production in LPS-induced macrophages, indicating improved anti-inflammatory efficacy over free curcumin. Conclusion: Curcumin-loaded PLGA nanoparticles show promise as a targeted drug delivery system, with enhanced stability, controlled release, and increased therapeutic efficacy. These findings support further in vivo studies to validate the clinical potential of curcumin nanoparticles in cancer and inflammatory diseases, providing a foundation for advanced therapeutic applications.

STING agonists and PI3Kγ inhibitor co-loaded ferric ion-punicalagin networks for comprehensive cancer therapy

Nanoparticles-based drug delivery system has been a promising approach for the treatment of colorectal cancer (CRC), which can be combined with chemotherapy, targeted therapy and immunotherapy to improve the treatment of CRC. 2′3’ cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) is an agonist of the STING signaling pathway activating antitumor immunity. IPI-549 is a small-molecule inhibitor for phosphatidylinositol 3-kinase γ (PI3Kγ), which can induce M1 macrophages polarization to provide pro-inflammatory microenvironment to suppress tumors. Here, we developed a ferric ion-punicalagin network (Fe-PU), which can be not only used as an inducer of ferroptosis, but also serve as a carrier to load cGAMP and IPI-549 to obtain nanohybrid (Fe-PU/CD-IPI). In order to improve the delivery effect and targeted ability to CRC, a cyclic arginine-glycine-aspartic acid peptide linked-bovine serum albumin were utilized to modify Fe-PU/CD-IPI to prepare nanohybrid Fe-PU/CD-IPI@cBSA. The therapeutic effect of various nanohybrids were validated in the mice with spontaneous tumor in the colorectal area and tumor-bearing mice, which lead to the increase of ferroptosis, the activation of STING signaling pathway, and the repolarization of macrophages. Collectively, the cGAMP and IPI-549 co-loaded nanohybrids effectively reshaped the tumor immune microenvironment, and exhibited prominent treatment effect of anti-colorectal cancer in vitro, patient-derived organoids, and in vivo.

Inhibitory impact of a mesoporous silica nanoparticle-based drug delivery system on Porphyromonas gingivalis-induced bone resorption

Controlling and reducing plaque formation plays a pivotal role in preventing and treating periodontal disease, often utilizing antibacterial drugs to enhance therapeutic outcomes. Mesoporous silica nanoparticles (MSN), an FDA-approved inorganic nanomaterial, possess robust physical and chemical properties, such as adjustable pore size and pore capacity, easy surface modification, and high biosafety. Numerous studies have exploited MSN to regulate drug release and facilitate targeted delivery. This study aimed to synthesize an MSN-tetracycline (MSN-TC) complex and investigate its inhibitory potential on Porphyromonas gingivalis (P. gingivalis)-induced bone resorption. The antibacterial efficacy of MSN-TC was evaluated through bacterial culture experiments. A P. gingivalis-induced bone resorption model was constructed by subcutaneously injecting P. gingivalis around the cranial bone of rats. Micro-computed tomography was employed to assess the inhibitory impact of MSN and MSN-TC on bone resorption. Furthermore, the influence of MSN and MSN-TC on osteoclast differentiation was examined in vitro. The MSN exhibited optimal pore size and particle dimensions for effective loading and gradual release of TC. MSN-TC demonstrated significant bacteriostatic activity against P. gingivalis. MSN-TC-treated rats showed significantly reduced cranial bone tissue destruction compared to MSN or TC-treated rats. Additionally, both MSN and MSN-TC exhibited inhibitory effects on the receptor activator of nuclear factor kappa-Β ligand-mediated osteoclast differentiation. The MSN-TC complex synthesized in this study demonstrated dual efficacy by exerting antibacterial effects on P. gingivalis and by resisting osteoclast differentiation, thereby mitigating bone resorption induced by P. gingivalis.Graphical

Optimized strategies for precise messenger RNA delivery using site-specific lipid nanoparticle-based drug delivery systems.

Optimized strategies for precise messenger RNA delivery using site-specific lipid nanoparticle-based drug delivery systems.

Nanotechnology-Driven Innovations in Malaria Treatment and Control: Current Challenges and Pharmaceutical Strategies

In the ongoing fight against malaria, an age-old disease responsible for hundreds of thousands of deaths annually, advancements in nanotechnology present new horizons for innovative interventions. This review provides a comprehensive review of the current state of nanotechnology-driven solutions in malaria treatment and control, outlining the ground-breaking opportunities they present and their challenges. Nanoparticle-based drug delivery systems have shown enhanced therapeutic efficacy, targeted delivery, and reduced side effects. Similarly, nanotechnology has paved the way for improved diagnostic tools with higher sensitivity and rapid detection capabilities. Furthermore, nano-enhanced vector control strategies have emerged, aiming to tackle malaria transmission at its source. Despite these advancements, challenges such as scale-up, biosafety, environmental concerns, and cost considerations persist. By bridging the gap between current challenges and pharmaceutical strategies, this review sheds light on the future direction of nanotechnology in malaria eradication, underscoring the potential it holds for revolutionizing the field and bringing us closer to a malaria-free world.

Scaling laws for nanoparticles – Online shape heterogeneity analysis by size exclusion chromatography coupled with multi-angle light scattering

Nanoparticle-based drug delivery systems are rising technologies to access challenging therapeutic targets. Following commercial success of lipid-based nanoparticles (LBNP), accruing understandings of nanoparticle structures and critical quality attributes through advanced analytics are beneficial to future clinical development and generalization of this delivery platform. The morphological attributes of nanoparticles, such as shape, can affect uptake, cell-interaction, drug release, circulation, and flow. Gaining an understanding of these structure-activity relationships in early-stage formulation development is important because mix morphologies can affect quality and potency but often exist before process control strategies are fully implemented. In this study, we used shape heterogeneous nanoparticle mixtures, containing various populations of liposomes and lipodisks, as a model system and developed an online semi-quantitative method to characterize the nanoparticle shape heterogeneity by size exclusion chromatography (SEC) coupled with multi-angle light scattering (MALS). The liposomes and lipodisks were separated in SEC when their sizes were ∼3 fold different. When the particles of different shapes were in similar sizes, size-based separation was not always feasible. Instead, light scattering data distinguished liposomes and lipodisks by the scaling law linking radius of gyration and molecular weight of the nanoparticles, enabling morphological identification. A semi-quantitative model was built based on the exponential correlation between the scaling law exponents and the ratios of liposomes and lipodisks. The model was applied to test 6 random formulations made with different compositions and manufacturing processes, and the predicted liposome percentage for 5 formulations was within 25 % absolute difference from the percentage determined by cryogenic electron microscopy (cryo-EM). We envision this method being routinely used to characterize liposome and lipodisk shape heterogeneity during formulation screening as well as on stability studies. Potentially, the method can be converted to in-process control method and extended to other categories of nanoparticles beyond liposomes.

A Minimal PBPK Model Describes the Differential Disposition of Silica Nanoparticles In Vivo.

Nanoparticles (NPs) have emerged as promising candidates for drug delivery due to their tunable physical and chemical properties. Among these, silica nanoparticles (SiNPs) are particularly valued for their biocompatibility and adaptability in applications like drug delivery and medical imaging. However, predicting SiNP biodistribution and clearance remains a significant challenge. To address this, we developed a minimal physiologically-based pharmacokinetic (mPBPK) model to simulate the systemic disposition of SiNPs, calibrated using in vivo PK data from mice. The model assesses how variations in surface charge, size, porosity, and geometry influence SiNP biodistribution across key organs, including the kidneys, lungs, liver, and spleen. A global sensitivity analysis identified the most influential parameters, with the unbound fraction and elimination rate constants for the kidneys and MPS emerging as critical determinants of SiNP clearance. Non-compartmental analysis (NCA) further revealed that aminated SiNPs exhibit high accumulation in the liver, spleen, and kidneys, while mesoporous SiNPs primarily accumulate in the lungs. Rod-shaped SiNPs showed faster clearance compared to spherical NPs. The mPBPK model was extrapolated to predict SiNP behavior in humans, yielding strong predictive accuracy with Pearson correlation coefficients of 0.98 for mice and 0.92 for humans. This model provides a robust framework for predicting the pharmacokinetics of diverse SiNPs, offering valuable insights for optimizing NP-based drug delivery systems and guiding the translation of these therapies from preclinical models to human applications.

Lipid-based nanoparticles: innovations in ocular drug delivery.

Ocular drug delivery presents significant challenges due to intricate anatomy and the various barriers (corneal, tear, conjunctival, blood-aqueous, blood-retinal, and degradative enzymes) within the eye. Lipid-based nanoparticles (LNPs) have emerged as promising carriers for ocular drug delivery due to their ability to enhance drug solubility, improve bioavailability, and provide sustained release. LNPs, particularly solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and cationic nanostructured lipid carriers (CNLCs), have emerged as promising solutions for enhancing ocular drug delivery. This review provides a comprehensive summary of lipid nanoparticle-based drug delivery systems, emphasizing their biocompatibility and efficiency in ocular applications. We evaluated research and review articles sourced from databases such as Google Scholar, TandFonline, SpringerLink, and ScienceDirect, focusing on studies published between 2013 and 2023. The review discusses the materials and methodologies employed in the preparation of SLNs, NLCs, and CNLCs, focusing on their application as proficient carriers for ocular drug delivery. CNLCs, in particular, demonstrate superior effectiveness attributed due to their electrostatic bioadhesion to ocular tissues, enhancing drug delivery. However, continued research efforts are essential to further optimize CNLC formulations and validate their clinical utility, ensuring advancements in ocular drug delivery technology for improved patient outcomes.

Progress in Research of Nanotherapeutics for Overcoming Multidrug Resistance in Cancer.

Chemotherapy has been widely applied in oncotherapy. However, the development of multidrug resistance (MDR) has diminished the effectiveness of anticancer drugs against tumor cells. Such resistance often results in tumor recurrence, metastasis, and patient death. Fortunately, nanoparticle-based drug delivery systems provide a promising strategy by codelivery of multiple drugs and MDR reversal agents and the skillful, flexible, smart modification of drug targets. Such systems have demonstrated the ability to bypass the ABC transporter biological efflux mechanisms due to drug resistance. Hence, how to deliver drugs and exert potential antitumor effects have been successfully explored, applied, and developed. Furthermore, to overcome multidrug resistance, nanoparticle-based systems have been developed due to their good therapeutic effect, low side effects, and high tumor metastasis inhibition. In view of this, we systematically discuss the molecular mechanisms and therapeutic strategies of MDR from nanotherapeutics. Finally, we summarize intriguing ideas and future trends for further research in overcoming MDR.

Exploring the potential of nanoparticles as a drug delivery system for cancer therapy: A review

In this review, we discuss the use of organic nanoparticles such as liposomes, polymeric nanoparticles, dendrimers, and inorganic nanoparticles such as gold nanoparticles and mesoporous silica nanoparticles in drug delivery in chemotherapy for cancer therapy. Another strategy is the use of nanoparticle vehicles for drug delivery through the natural openings on tumor vessels called fenestrations. Both of these can be functionalized to attach angiotensin to lymphocytes or any certain part of the cancer cell membrane, microenvironment, or cytoplasmic or nuclear receptor sites, and therefore a high concentration of drug delivery to targeted cancer cells is achieved, but with less or no toxicity to normal tissue. The potential advantages evident in this technology are useful approaches to established high-concentration drug treatment of cancer tissues without harming normal cells. Some features of a nanoparticle-based drug delivery system include the durability of the vehicle, biocompatibility, permeation, and ability to target specific types of cells. Organic and inorganic nanoparticles have developed this kind of drug-carrier system. Particulate systems are also still being explored for cancer drug resistance mechanisms, and their function in immunotherapy is expanding.

PH/Hypoxia dual-stimuli responsive COF nanocarriers with reversible charge conversions for the accurate tumor-targeting and enhanced anticancer drug delivery

Nanoparticles-based drug delivery systems show great promise for cancer therapy due to the advantages of crossing physiological barrier, high drug availability and good stability. However, deep tumor penetration, long blood circulation, and rapid drug release remain intractable problems for nanocarriers. In this work, we report a tumor microenvironment-sensitive nanodrug delivery system containing both acidic pH and hypoxia response sites to achieve enhanced drug permeability and on-demand release for precise cancer therapy. The covalent organic frameworks (COFs) with introduced azobenzene (azo) groups were used as employed as nanocarrier, and modified by pH-sensitive sulfamide-based zwitterionic polymers (PBA), followed by loading with the chemotherapeutic drug doxorubicin (DOX) to obtain COF-PBA@DOX. Copolymer PBA achieved charge conversions in tumor acidic environment, resulting in a positive charge on the nanocarrier surfaces, thus facilitating the augmented tumor accumulation. Meanwhile, azo which was formed the COF carrier, could be reduced to amines by the highly expressed azoreductase under tumor hypoxia conditions, resulting in nanoparticle dissociation and the drug-controlled release at the solid tumor sites. The fabricated dual-responsive nanomedicine, based on the surface charge-reversal of zwitterion in the acidic environment of tumor, can realize the accumulation and targeted drug release at the tumor site, which has great potential as a nanocarrier in tumor therapy.