Molecular Pharmaceutics最新文献

{"title":"Noninvasive Imaging of Immune Cell Activity in Myocardial Infarction Phases Using ^99mTc-HYNIC-mAb_Kv1.3 SPECT/CT.","authors":"Zhengyan Wang, Xiangming Song, Sixuan Cheng, Dawei Jiang, Danzhan Zheng, Xiaoli Lan, Kun Liu, Cheng Fan","doi":"10.1021/acs.molpharmaceut.4c00966","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c00966","url":null,"abstract":"<p><p>Acute myocardial infarction (MI) remains a leading cause of mortality worldwide, with inflammatory and reparative phases playing critical roles in disease progression. Currently, there is a pressing need for <i>in vivo</i> imaging techniques to monitor immune cell infiltration and inflammation activity during these phases. We developed a novel probe, ^99mTc-HYNIC-mAb_Kv1.3, utilizing a monoclonal antibody that targets the voltage-gated potassium channel 1.3 (Kv1.3). This probe enables <i>in vivo</i> visualization of immune cells that express high levels of Kv1.3 proteins. In a murine MI model, SPECT/CT imaging with ^99mTc-HYNIC-mAb_Kv1.3 demonstrated specific uptake in an infarcted myocardium during the inflammatory phase, reflecting immune cell infiltration and activity. During the reparative phase, the probe exhibited prolonged retention in the infarcted area, suggestive of ongoing immune cell proliferation. Immunofluorescence staining confirmed the probe's specificity. Biodistribution analysis indicated preferential accumulation in the infarcted myocardium and liver, consistent with SPECT/CT findings. Combined with [¹⁸F]FDG PET/CT, these modalities provided comprehensive insights into myocardial viability and inflammation. This study highlights the potential of ^99mTc-HYNIC-mAb_Kv1.3 SPECT/CT as a noninvasive tool to monitor immune cell activity in different phases of MI, guide therapeutic interventions, and predict disease progression. Further translational studies are warranted to explore its clinical applicability in cardiac pathologies.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage Membrane-Cloaked ROS-Responsive Albumin Nanoplatforms for Targeted Delivery of Curcumin to Alleviate Acute Liver Injury.","authors":"Dandan Hu, Zhenqiu Huang, Wenlong Li, Lianhai Shan, Ming-Yu Wu, Shun Feng, Yu Wan","doi":"10.1021/acs.molpharmaceut.4c00808","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c00808","url":null,"abstract":"<p><p>Developing low-toxicity, high-efficacy, and fast-acting strategies to manage acute liver injury (ALI) is critical due to its rapid progression and potential for severe outcomes. Curcumin (CUR) has shown promise in ALI therapy due to its ability to modulate the inflammatory microenvironment by scavenging reactive oxygen species (ROS). Nevertheless, CUR is highly hydrophobic limiting its bioavailability and effective in vivo transport, which hinders its further application. In this study, we developed an inflammatory microenvironment-targeted drug delivery system by covalently coupling human serum albumin (HSA) with ROS-sensitive thioketal linkers and loading it with CUR to form nanoparticles (HSA-TK/CUR). These nanoparticles were then coated with a macrophage membrane (CM@HSA-TK/CUR), resulting in negatively charged spherical particles (≈ -23.26 mV) with an average particle size of around 165 nm. ROS responsiveness was confirmed through drug release assays and enhanced ROS depletion was further demonstrated by Diacetyldichlorofluorescein (DCFH-DA) ROS detection experiments. CM@HSA-TK/CUR treatment resulted in a 94.7% reduction in ROS levels in inflammatory cells. In addition, cellular uptake and in vivo distribution experiments demonstrated that camouflaging HSA-TK/CUR with macrophage membranes significantly enhanced its targeting of the inflammatory microenvironment. The findings revealed that CM@HSA-TK/CUR rapidly accumulated in the injured liver within 6 h, inhibited the production of pro-inflammatory factors (IL-1β, IL-6, and TNF-α), shifted macrophage polarization from M1 to M2 in vivo, and protected hepatocytes from oxidative stress-associated cell death, significantly attenuating the inflammatory response in ALI mice. In conclusion, CM@HSA-TK/CUR has excellent potential in treating mice with ALI.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melanin-Binding-Based Discovery of Topically Instilled Carbonic Anhydrase Inhibitors for Targeted Delivery and Prolonged Action in the Eye.","authors":"Annika Valtari, Stanislav Kalinin, Janika Jäntti, Pekka Vanhanen, Martina Hanzlikova, Arun Tonduru, Katja Stenberg, Tapani Viitala, Kati-Sisko Vellonen, Elisa Toropainen, Marika Ruponen, Arto Urtti","doi":"10.1021/acs.molpharmaceut.4c00694","DOIUrl":"10.1021/acs.molpharmaceut.4c00694","url":null,"abstract":"<p><p>Glaucoma is a vision-threatening disease that is currently treated with intraocular-pressure-reducing eyedrops that are instilled once or multiple times daily. Unfortunately, the treatment is associated with low patient adherence and suboptimal treatment outcomes. We developed carbonic anhydrase II inhibitors (CAI-II) for a prolonged reduction of intraocular pressure (IOP). The long action is based on the melanin binding of the drugs that prolongs ocular drug retention and response. Overall, 63 new CAI-II compounds were synthesized and tested for melanin binding in vitro. Carbonic anhydrase affinity and IOP reduction of selected compounds were tested in rabbits. Prolonged reduction of IOP in pigmented rabbits was associated with increasing melanin binding of the compound. Installation of a single eye drop of a high melanin binder carbonic anhydrase inhibitor (CAI) resulted in ≈2 weeks' decrease of IOP, whereas the effect lasted less than 8 h in albino rabbits. Duration of the IOP response correlated with melanin binding of the compounds. Ocular pharmacokinetics of a high melanin binder compound was studied after eye drop instillation to the rat eyes. The CAI showed prolonged drug retention in the pigmented iris-ciliary body but was rapidly eliminated from the albino rat eyes. The melanin-bound drug depot maintained effective free concentrations of CAI in the ciliary body for several days after application of a single eye drop. In conclusion, melanin binding is a useful tool in the discovery of long-acting ocular drugs.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-Repopulating Cell-Derived Microparticle-Based Therapeutics Amplify the Antitumor Effect through Synergistic Inhibition of Chemoresistance and Immune Evasion.","authors":"Nana Bie, Shiyu Li, Qingle Liang, Wenxia Zheng, Shiyi Xu, Haojie Liu, Xiaojuan Zhang, Zhaohan Wei, Tuying Yong, Xiangliang Yang, Lu Gan","doi":"10.1021/acs.molpharmaceut.4c00709","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c00709","url":null,"abstract":"<p><p>Traditional chemotherapy often encounters failure attributed to drug resistance mediated by tumor-repopulating cells (TRCs) and chemotherapy-triggered immune suppression. The effective inhibition of TRCs and the mitigation of drug-induced immune suppression are pivotal for the successful chemotherapy. Here, TRC-derived microparticles (3D-MPs), characterized by excellent tumor-targeting and high TRC uptake properties, are utilized to deliver metformin and the chemotherapeutic drug doxorubicin ((DOX+Met)@3D-MPs). (DOX+Met)@3D-MPs efficiently enhance tumor accumulation and are highly internalized in tumor cells and TRCs. Additionally, (DOX+Met)@3D-MPs significantly decrease the chemotherapy-triggered upregulation in P-glycoprotein expression to enhance intracellular doxorubicin retention, resulting in increased chemotherapy sensitivity and immunogenic cell death in tumor cells and TRCs for improved antitumor immunity. Importantly, (DOX+Met)@3D-MPs also remarkably reduce chemotherapy-induced PD-L1 expression, efficiently alleviating immune suppression facilitated by the PD-L1/PD-1 axis to further enhance immunological response against malignancy. These results underscore the (DOX+Met)@3D-MPs' potential as a viable platform for augmenting the efficacy of antitumor therapies.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of ^99mTc-Labeled Complexes with a Niraparib HYNIC Derivative for PARP-Positive Tumor Imaging.","authors":"Qianna Wang, Junhong Feng, Yuhao Jiang, Qing Ruan, Guangxing Yin, Peiwen Han, Junbo Zhang","doi":"10.1021/acs.molpharmaceut.4c01237","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01237","url":null,"abstract":"<p><p>As an enzyme that plays an important role in DNA repair, poly(ADP-ribose) polymerase-1 (PARP-1) has become a popular target for cancer therapy. Nuclear medicine molecular imaging technology, supplemented by radiolabeled PARP-1 inhibitors, can accurately determine the expression level of PARP-1 at lesion sites to help patients choose an appropriate treatment plan. In this work, niraparib was modified with a hydrazinonicotinamide (HYNIC) group to generate the ligand NPBHYNIC, which has an <i>in vitro</i> affinity (IC₅₀) of 450.90 nM for PARP-1. The ligand NPBHYNIC was labeled with technetium-99m and six different coligands to yield [^99mTc]Tc-(<i>X</i>/tricine)-NPBHYNIC (<i>X</i> = TPPTS, TPPMS, PSA, PDA, NIC and ISONIC). These complexes were hydrophilic and exhibited good stability <i>in vitro</i>, and low levels of these complexes were taken up by nontarget organs and tissues in Kunming mice. Among these complexes, [^99mTc]Tc-(TPPTS/tricine)-NPBHYNIC and [^99mTc]Tc-(NIC/tricine)-NPBHYNIC were selected for biodistribution in HeLa tumor-bearing BALB/c nude mice at 2 h post injection. The results revealed that the tumor uptake of [^99mTc]Tc-(TPPTS/tricine)-NPBHYNIC (1.02 ± 0.07% ID/g) was greater than that of [^99mTc]Tc-(NIC/tricine)-NPBHYNIC (0.36 ± 0.05% ID/g). Additionally, in biodistribution, single-photon emission computed tomography/computed tomography (SPECT/CT) and radioautography experiments, the tumor uptake of [^99mTc]Tc-(TPPTS/tricine)-NPBHYNIC was significantly reduced in the blocked group, indicating PARP-1 specificity. Therefore, it has potential for use as a niraparib-based tumor imaging agent that targets PARP-1.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Antituberculosis Treatment Nanoparticles Encapsulated with Catalase and Levofloxacin Under Ultrasound Stimulation: A 3D Spheroid Study.","authors":"Jiajun Guo, Yan Qiu, Can Hu, Yuchao Cao, Dairong Li, Yonghong Du","doi":"10.1021/acs.molpharmaceut.4c00748","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c00748","url":null,"abstract":"<p><p>Tuberculosis (TB) is a chronic infectious disease caused by <i>Mycobacterium tuberculosis</i> (MTB). Tuberculous granuloma is the central and key pathological structure of tuberculosis and is characterized by tissue hypoxia and ineffective drug delivery. To address these issues, this study fabricated a composite nanoparticle loaded with catalase (CAT) and levofloxacin (LEV) (CAT@LEV-NPs) and then combined it with ultrasound (US) to investigate the bactericidal effect and underlying mechanisms using TB spheroids. The TB spheroids were constructed using attenuated Bacillus Calmette-Guérin (BCG) instead of MTB to facilitate operation under general experimental conditions. This study examined the physical properties and oxygen production efficiency of CAT@LEV-NPs. Subsequently, we treated TB spheroids with nanoparticles alone or in combination with US and found that ultrasound significantly increased drug permeability and activated CAT@LEV-NPs to produce a large number of reactive oxygen species (ROS). The combined treatment showed excellent antibacterial effects, resulting in more severe damage to the bacterial structure than other treatments. Additionally, the combined treatment induced a higher M1 polarization of macrophages, increased the apoptosis rate, and improved the anoxic microenvironment in TB spheroids. These factors may be closely related to the enhanced bactericidal effects of combined treatment. In conclusion, our study suggests that US combined with CAT@LEV-NPs could serve as a novel, noninvasive, safe, and effective treatment modality for intractable MTB infections.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A New Analytical Method for Quantifying Acid-End-Cap PLGA in Sub-Milligram Quantities.","authors":"John Garner, Sarah Skidmore, Gary Overdorf, Justin Hadar, Haesun Park, Kinam Park, Yan Wang, Young Kuk Jhon, William C Smith, Deyi Zhang, Yuan Zou","doi":"10.1021/acs.molpharmaceut.4c01057","DOIUrl":"10.1021/acs.molpharmaceut.4c01057","url":null,"abstract":"<p><p>Characterization of PLGA polymers used in FDA-approved drug products is critical for quality control and qualitative/quantitative (Q1/Q2) evaluation of potential generic formulations. Various techniques have been developed and used to characterize the molecular properties of PLGA polymers, such as molecular weight, molecular composition, and molecular structure. Commonly used techniques include gel permeation chromatography (GPC), nuclear magnetic resonance (NMR), semisolvent methods, and GPC-based intrinsic viscosity measurement. It is noted that the existing analytical methods may not be able to separate and quantify PLGA polymers when used as a mixture in a drug product (e.g., Durysta and Ozurdex). In particular, one assay method still lacking is quantitating the PLGA polymer with acid-end-cap (PLGA-A) in the mixture containing PLGA with ester-end-cap (PLGA-E), especially when the sample quantity is below the submilligram level. The total PLGA quantities available in Durysta and Ozurdex formulations are too small (<1 mg) to use existing assay methods to quantify the PLGA-A content. A new assay method was developed to quantitate PLGA-A in the mixture with PLGA-E. The acid end-cap was modified with pyrene methylamine (a UV dye) to enhance the signal and compared with the total PLGA quantity measured with the refractive index (RI) after a sample was run through a GPC. This GPC-UV/RI approach is based on measuring the total acid number (TAN) of PLGA-A and converting it to the PLGA-A quantity to compare with the total PLGA. Unlike conventional methods of measuring TAN, the GPC-UV/RI methods enables TAN measurements of submilligram PLGA quantities. Application of this method to Ozurdex-similar samples showed the expected acid:ester ratio of PLGAs. This new approach provides another powerful tool for characterizing PLGA polymers in FDA-approved drug products. This is especially significant considering that the PLGAs of commercial products are likely to have molecular properties different from those of the raw PLGAs before going through the manufacturing process.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"446-458"},"PeriodicalIF":4.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression-Dependent Tumor Pretargeting via Engineered Avidity.","authors":"Abbigael Harthorn, Tse-Han Kuo, Sarah W Torres, Roy R Lobb, Benjamin J Hackel","doi":"10.1021/acs.molpharmaceut.4c01177","DOIUrl":"10.1021/acs.molpharmaceut.4c01177","url":null,"abstract":"<p><p>Selective delivery of therapeutic modalities to tumor cells via binding of tumor-selective cell-surface biomarkers has empowered substantial advances in cancer treatment. Yet, tumor cells generally lack a truly specific biomarker that is present in high density on tumor tissue while being completely absent from healthy tissue. Rather, low but nonzero expression in healthy tissues results in on-target, off-tumor activity with detrimental side effects that constrain the therapeutic window or prevent use altogether. Advanced technologies to enhance the selectivity for tumor targeting are sorely needed. We have engineered a binding platform that is quantitatively dependent upon expression levels, via avidity-driven specificity, rather than binarily reliant on the presence or absence of a biomarker. We systematically varied monomeric binding affinity by engineering affibodies to target carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and folate receptor 1 (FolR1). Two identical affibody ligands were tethered, with varying polypeptide linker lengths, to a nanobody that binds Alfa peptide to create a bispecific, trivalent protein for use in pretargeted radioligand therapy. Expression-dependent targeting was achieved in both systems: with 110 nM monomeric affinity to CEACAM5 with a two-amino-acid linker or with 250 nM monomeric affinity for FolR1 and a 10 amino acid linker. The latter bispecific, trivalent achieved over 25-fold differentiation between FolR1^high and FolR1^low cells in a mixed culture. Similar selectivity was achieved in a size-efficient bivalent molecule lacking a central nanobody. Moreover, the avid bivalent affibody molecule exhibited minimal inhibition by soluble antigen, whereas high-affinity bivalent antibody was inhibited by 97 ± 2%, which is indicative of serum inhibition of shed antigen. This work advances design principles for achieving expression-dependent tumor targeting via low-affinity, high-avidity ligands.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"558-572"},"PeriodicalIF":4.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Announcing the Winners of the 2025 <i>Molecular Pharmaceutics</i> Early Career Best Paper Award.","authors":"Lynne S Taylor","doi":"10.1021/acs.molpharmaceut.4c01444","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01444","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 1","pages":"3-4"},"PeriodicalIF":4.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracranial Nanogel Pellets Carrying Temozolomide and Paclitaxel for Adjuvant Brain Cancer Therapy.","authors":"Hasan Slika, Aanya Shahani, Kranthi Gattu, Varsha Mundrathi, Ameilia A Solan, Brianna Gonzalez, Tasmima N Haque, Sadia Rahman, Vrashabh V Sugandhi, Jennifer Lee, Esteban Velarde, Safwan Alomari, Victor Lance Pacis, Henry Brem, Betty Tyler, Xiaoban Xin, Hyunah Cho","doi":"10.1021/acs.molpharmaceut.4c00708","DOIUrl":"10.1021/acs.molpharmaceut.4c00708","url":null,"abstract":"<p><p>Glioblastoma multiforme is the most frequently diagnosed primary malignant brain tumor. Despite multimodal therapy with surgical resection, radiation therapy, and chemotherapy, recurrence of the tumor is almost always guaranteed due to the infiltrative nature of the disease. Moreover, the blood brain barrier imparts an additional layer of complexity by impeding the delivery of therapeutic agents to the tumor, hence limiting the efficacy of systemically delivered drugs. Hence, to overcome this obstacle and avoid treatment resistance, the local delivery of combination therapies has risen as an appealing adjuvant treatment. The present study describes the creation of a novel PLGA-PEG-PLGA-based nanogel pellet system for the interstitial delivery of Temozolomide (TMZ) and paclitaxel (PTX) to the brain. The nanogel pellet was shown to be stable as a pellet at ambient temperature, absorb water, change to a gel formulation at physiological temperature, and achieve gradual long-term release of TMZ and PTX in vitro. Additionally, in vivo testing of the TMZ/PTX-loaded nanogel pellets in an orthotopic CT2A mouse model and an orthotopic 9L rat model has shown an acceptable safety profile when implanted intracranially and a significant improvement in overall survival.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"131-141"},"PeriodicalIF":4.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}