Tumor-Acidity Responsive Polymeric Nanoparticles for Targeting Delivery of Angiogenesis Inhibitor for Enhanced Antitumor Efficacy With Decreased Toxicity

Various nanocarriers with tumor targeting ability and improved pharmacokinetic property have been extensively utilized to reduce the toxicity of existing clinical chemotherapeutics. Herein, we showed that by encapsulating angiogenesis inhibitor anlotinib into polymeric nanoparticles, we could significantly decrease its in vivo toxicity. The introduction of pH-responsiveness into the nanocarrier further enhanced its anti-tumor activity. Systemic administration of the anlotinib-loaded nanocarrier into mice bearing A549 and 4T1 subcutaneous tumor received a higher tumor growth suppression and metastasis inhibition without detectable side effects. This strategy offers a promising option to improve the patient compliance of anlotinib.

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A Novel TMTP1-modified Theranostic Nanoplatform for Targeted in Vivo NIR-II Fluorescence Imaging-guided Chemotherapy of Cervical Cancer

10.21203/rs.3.rs-818556/v1 ◽

2021 ◽

Author(s):

Alifu Nuernisha ◽

Rong Ma ◽

Lijun Zhu ◽

Zhong Du ◽

Shuang Chen ◽

...

Keyword(s):

Cervical Cancer ◽

Blood Vessels ◽

Fluorescence Imaging ◽

Spatial Resolution ◽

Self Assembly ◽

Tumor Targeting ◽

High Sensitivity ◽

High Definition ◽

Targeting Ability

Abstract BackgroundNear-infrared II (NIR-II, 900-1700 nm) fluorescence bioimaging with advantages of good biosafety, excellent spatial resolution, high sensitivity and contrast, has attracted great attentions in biomedical research fields. However, most nanoprobes used for NIR-II fluorescence imaging have poor tumor-targeting ability and therapeutic efficiency. To overcome these limitations, a novel NIR-II-emissive theranostic nanoplatform for imaging and treatment of cervical cancer was designed and prepared. The NIR-II-emissive dye IR-783 and chemotherapy drug doxorubicin (DOX) were encapsulated into liposomes, and the tumor-targeting peptide TMTP1 was conjugated to the surface of the liposomes to form IR-783-DOX-TMTP1 nanoparticles (NPs) via self-assembly methods.ResultsThe IR-783-DOX-TMTP1 NPs showed strong NIR-II emission, excellent biocompatibility, a long lifetime, and low toxicity. Further, high-definition NIR-II fluorescence microscopy images of ear blood vessels and intratumor blood vessels were obtained from IR-783-DOX-TMTP1 NPs-stained mice with high spatial resolution under 808 nm laser excitation. Moreover, IR-783-DOX-TMTP1 NPs showed strong tumor targeting ability and high efficiently chemotherapeutic character towards cervical tumors. ConclusionsThe novel targeting and NIR-II-emissive IR-783-DOX-TMTP1 NPs have potential in diagnosis and therapy for cervical cancer.

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Targeted Delivery Prodigiosin to Choriocarcinoma by Peptide-Guided Dendrigraft Poly-l-lysines Nanoparticles

International Journal of Molecular Sciences ◽

10.3390/ijms20215458 ◽

2019 ◽

Vol 20 (21) ◽

pp. 5458 ◽

Cited By ~ 2

Author(s):

Kai Zhao ◽

Dan Li ◽

Guogang Cheng ◽

Baozhen Zhang ◽

Jinyu Han ◽

...

Keyword(s):

Targeted Delivery ◽

Tumor Targeting ◽

Caspase 3 ◽

Slow Release ◽

Normal Cells ◽

Binding Peptide ◽

P53 Signaling ◽

Targeting Delivery ◽

P53 Signaling Pathway

The available and effective therapeutic means to treat choriocarcinoma is seriously lacking, mainly due to the toxic effects caused by chemotherapy and radiotherapy. Accordingly, we developed a method for targeting delivery of chemotherapeutical drugs only to cancer cells, not normal cells, in vivo, by using a synthetic placental chondroitin sulfate (CSA)-binding peptide (plCSA-BP) derived from malarial protein VAR2CSA. A 28 amino acids placental CSA-binding peptide (plCSA-BP) from the VAR2CSA was synthesized as a guiding peptide for tumor-targeting delivery, dendrigraft poly-L-lysines (DGL) was modified with plCSA-BP and served as a novel targeted delivery carrier. Choriocarcinoma was selected to test the effect of targeted delivery carrier, and prodigiosin isolated from Serratia marcescens subsp. lawsoniana was selected as a chemotherapeutical drug and encapsulated in the DGL modified by the plCSA-BP nanoparticles (DGL/CSA-PNPs). DGL/CSA-PNPs had a sustained slow-release feature at pH 7.4, which could specifically bind to the JEG3 cells and exhibited better anticancer activity than that of the controls. The DGL/CSA-PNPs induced the apoptosis of JEG3 cells through caspase-3 and the P53 signaling pathway. DGL/CSA-PNPs can be used as an excellent targeted delivery carrier for anticancer drugs, and the prodigiosin could be an alternative chemotherapeutical drug for choriocarcinoma.

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Novel vinyl-modified RGD conjugated silica nanoparticles based on photo click chemistry for in vivo prostate cancer targeted fluorescence imaging

RSC Advances ◽

10.1039/c9ra04513a ◽

2019 ◽

Vol 9 (44) ◽

pp. 25318-25325

Author(s):

Hanrui Li ◽

Ke Li ◽

Qi Zeng ◽

Yun Zeng ◽

Dan Chen ◽

...

Keyword(s):

Prostate Cancer ◽

Click Chemistry ◽

Silica Nanoparticles ◽

Fluorescence Imaging ◽

Tumor Targeting ◽

Diagnosis And Treatment ◽

Targeting Ability

Photo click chemistry has been used to prepare RGD conjugated silica nanoprobe (SiO2@T1-RGDk NPs) that exhibits excellent tumor targeting ability and negligible toxicity which enables them to be used for the diagnosis and treatment of cancer.

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Light-Responsive Micelles Loaded With Doxorubicin for Osteosarcoma Suppression

Frontiers in Pharmacology ◽

10.3389/fphar.2021.679610 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jiayi Chen ◽

Chenhong Qian ◽

Peng Ren ◽

Han Yu ◽

Xiangjia Kong ◽

...

Keyword(s):

Cellular Uptake ◽

Blood Circulation ◽

Tumor Targeting ◽

Polymeric Micelles ◽

Polymeric Nanoparticles ◽

Amide Bond ◽

Significant Damage ◽

Stimulus Responsive ◽

Significant Factors

The enhancement of tumor targeting and cellular uptake of drugs are significant factors in maximizing anticancer therapy and minimizing the side effects of chemotherapeutic drugs. A key challenge remains to explore stimulus-responsive polymeric nanoparticles to achieve efficient drug delivery. In this study, doxorubicin conjugated polymer (Poly-Dox) with light-responsiveness was synthesized, which can self-assemble to form polymeric micelles (Poly-Dox-M) in water. As an inert structure, the polyethylene glycol (PEG) can shield the adsorption of protein and avoid becoming a protein crown in the blood circulation, improving the tumor targeting of drugs and reducing the cardiotoxicity of doxorubicin (Dox). Besides, after ultraviolet irradiation, the amide bond connecting Dox with PEG can be broken, which induced the responsive detachment of PEG and enhanced cellular uptake of Dox. Notably, the results of immunohistochemistry in vivo showed that Poly-Dox-M had no significant damage to normal organs. Meanwhile, they showed efficient tumor-suppressive effects. This nano-delivery system with the light-responsive feature might hold great promises for the targeted therapy for osteosarcoma.

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An internal cross-linked polymeric nanoparticle with dual sensitivity for combination therapy of muscle-invasive bladder cancer

10.21203/rs.3.rs-29953/v3 ◽

2020 ◽

Author(s):

Guanchen Zhu ◽

Kaikai Wang ◽

Haixiang Qin ◽

Xiaozhi Zhao ◽

Wei Chen ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Cells ◽

Laser Irradiation ◽

Tumor Cells ◽

Tumor Targeting ◽

Near Infrared ◽

Infrared Laser ◽

Infrared Laser Irradiation ◽

Targeting Ability

Abstract Chemotherapy is a standard cancer treatment which uses anti-cancer drugs to destroy or slow the growth of cancer cells. However, chemotherapy has limited therapeutic effects in bladder cancer. One of the reasons of this resistance to chemotherapy is that higher levels of glutathione in invasive bladder cancer cells. We have fabricated nanoparticles that respond to high concentrations of glutathione and near-infrared laser irradiation in order to increase the drug accumulation at the tumor sites and combine chemotherapy with photothermal therapy to overcome the challenges of bladder cancer treatment.Methods:The DOX&IR780@PEG-PCL-SS NPs were prepared by co-precipitation method. We investigated the tumor targeting capability of NPs in vitro and in vivo. The orthotopic bladder cancer model in C57BL/6 mice was established for in vivo study and the photothermal effects and therapeutic efficacy of NPs were evaluated.Results:The DOX&IR780@PEG-PCL-SS NPs were synthesized using internal cross-linking strategy to increase the stability of nanoparticles. Nanoparticles can be ingested by tumor cells in a short time. The DOX&IR780@PEG-PCL-SS NPs have dual sensitivity to high levels of glutathione in bladder cancer cells and near-infrared laser irradiation. Glutathione triggers chemical structural changes of nanoparticles and preliminarily releases drugs, Near-infrared laser irradiation can promote the complete release of the drugs from the nanoparticles and induce a photothermal effect, leading to destroying the tumor cells. Given the excellent tumor-targeting ability and negligible toxicity to normal tissue, DOX&IR780@PEG-PCL-SS NPs can greatly increase the concentration of the anti-cancer drugs in tumor cells. The mice treated with DOX&IR780@PEG-PCL-SS NPs have a significant reduction in tumor volume. The DOX&IR780@PEG-PCL-SS NPs can be tracked by in vivo imaging system and have good tumor targeting ability, to facilitate our assessment during the experiment.Conclusion:A nanoparticle delivery system with dual sensitivity to glutathione and near-infrared laser irradiation was developed for delivering IR780 and DOX. Chemo-photothermal synergistic therapy of both primary bladder cancer and their metastases was achieved using this advanced delivery system.

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Intravenous, Intraperitoneal, and Subcutaneous Routes of Administering 64Cu-DOTA-HB22.7 Display Equivalent Tumor Targeting Ability.

Blood ◽

10.1182/blood.v110.11.2359.2359 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2359-2359

Author(s):

Shiloh M. Martin ◽

Robert T. O’Donnell ◽

Hayes McKnight ◽

Julie L. Sutcliff ◽

Joseph M. Tuscano

Keyword(s):

Nude Mice ◽

Tumor Targeting ◽

Emission Tomography ◽

New Agents ◽

Routes Of Administration ◽

Positron Emission ◽

Specific Tumor ◽

Human Lymphoma ◽

Targeting Ability

Abstract BACKGROUND: Chemotherapy for Non-Hodgkin’s Lymphoma (NHL) is initially effective, but often limited by toxicity and resistance. New agents for the treatment of NHL are needed. HB22.7 is a monoclonal antibody that binds CD22 and has previously been shown to reduce human lymphoma xenograft volume in nude mice. OBJECTIVES: (1) Develop a 64Cu-DOTA-HB22.7 antibody, for in vivo imaging and potential therapy of NHL. (2) Determine if tumor targeting of 64Cu-DOTA-HB22.7 is equivalent between intravenous (IV), intraperitoneal (IP), and subcutaneous (SQ) routes of administration. METHODS: DOTA-HB22.7’s ability to bind CD22+ cells was assessed by flow cytometry. 64Cu-DOTA-HB22.7 was injected IV, IP, or SQ into xenograft-bearing nude mice and tumor targeting assessed by positron emission tomography (PET) and biodistribution assay. Pharmacokinetics were determined by measuring radioactivity of blood samples. Serum was analyzed by radio-TLC. RESULTS: DOTA conjugation does not affect HB22.7’s ability to bind CD22. 64Cu-DOTA-HB22.7 demonstrates specific tumor targeting at 24 and 48 hrs. Targeting is equivalent regardless of route of administration. Pharmacokinetics demonstrate that 64Cu-DOTA-HB22.7 can access the bloodstream (and thus, target tumor) in IP or SQ injections. By 48 hrs, blood 64Cu levels are (a) equivalent, regardless of injection route and (b) below peak levels, indicating clearance from the circulation. Serum analysis shows that right-shifted TLC peaks, possibly 64Cu-DOTA-HB22.7 metabolites, are present only in the IV injected group at 48 hrs. CONCLUSION: These findings establish 64Cu-DOTA-HB22.7 as an NHL-specific imaging agent and indicate its potential for use in radioimmunotherapy. These findings provide evidence that more accessible routes of administration can achieve equivalent targeting results, and may lead to more efficient and accurate administration of antibody-based therapeutics in mice.

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A folic acid conjugated polyethylenimine-modified PEGylated nanographene loaded photosensitizer: photodynamic therapy and toxicity studies in vitro and in vivo

Journal of Materials Chemistry B ◽

10.1039/c6tb00108d ◽

2016 ◽

Vol 4 (12) ◽

pp. 2190-2198 ◽

Cited By ~ 10

Author(s):

Yi-Ping Zeng ◽

Sheng-Lin Luo ◽

Zhang-You Yang ◽

Jia-Wei Huang ◽

Hong Li ◽

...

Keyword(s):

Photodynamic Therapy ◽

Folic Acid ◽

Delivery System ◽

Tumor Targeting ◽

Therapy Efficacy ◽

Toxicity Studies ◽

Targeting Delivery

A novel nanographene-based tumor-targeting delivery system has high photodynamic therapy efficacy with no obvious toxicity and could potentially be utilized in biomedicine.

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Platelet-derived porous nanomotor for thrombus therapy

Science Advances ◽

10.1126/sciadv.aaz9014 ◽

2020 ◽

Vol 6 (22) ◽

pp. eaaz9014 ◽

Cited By ~ 13

Author(s):

Mimi Wan ◽

Qi Wang ◽

Rongliang Wang ◽

Rui Wu ◽

Ting Li ◽

...

Keyword(s):

Near Infrared ◽

In Vivo Evaluation ◽

Macroporous Silica ◽

Rapid Release ◽

Anticoagulant Drugs ◽

Targeting Delivery ◽

Targeting Ability ◽

Sequential Drug Release

The treatment difficulties of venous thrombosis include short half-life, low utilization, and poor penetration of drugs at thrombus site. Here, we develop one kind of mesoporous/macroporous silica/platinum nanomotors with platelet membrane (PM) modification (MMNM/PM) for sequentially targeting delivery of thrombolytic and anticoagulant drugs for thrombus treatment. Regulated by the special proteins on PM, the nanomotors target the thrombus site and then PM can be ruptured under near-infrared (NIR) irradiation to achieve desirable sequential drug release, including rapid release of thrombolytic urokinase (3 hours) and slow release of anticoagulant heparin (>20 days). Meantime, the motion ability of nanomotors under NIR irradiation can effectively promote them to penetrate deeply in thrombus site to enhance retention ratio. The in vitro and in vivo evaluation results confirm that the synergistic effect of targeting ability from PM and motion ability from nanomotors can notably enhance the thrombolysis effect in both static/dynamic thrombus and rat model.

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Aza-crown ether locked on polyethyleneimine: solving the contradiction between transfection efficiency and safety during in vivo gene delivery

Chemical Communications ◽

10.1039/c9cc10041e ◽

2020 ◽

Vol 56 (41) ◽

pp. 5552-5555

Author(s):

Shengran Li ◽

Lin Lin ◽

Wenliang Wang ◽

Xinxin Yan ◽

Binggang Chen ◽

...

Keyword(s):

Gene Delivery ◽

Crown Ether ◽

Tumor Targeting ◽

Transfection Efficiency ◽

High Gene ◽

In Vivo Gene Delivery ◽

Targeting Ability ◽

Extended Circulation ◽

Aza Crown Ether

An aza-crown ether derivative to lock a hyperbranched PEI, which endows the PEI with tumor targeting ability, antiserum ability and extended circulation in the blood, meanwhile retaining the high gene complexation and high transfection efficiency.

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Cisplatin Loaded Hyaluronic Acid Modified TiO2Nanoparticles for Neoadjuvant Chemotherapy of Ovarian Cancer

Journal of Nanomaterials ◽

10.1155/2015/390358 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Enling Liu ◽

Yuxiu Zhou ◽

Zheng Liu ◽

Jun Li ◽

Donghong Zhang ◽

...

Keyword(s):

Ovarian Cancer ◽

Hyaluronic Acid ◽

Neoadjuvant Chemotherapy ◽

Tumor Targeting ◽

Ovarian Cancer Cells ◽

Release Property ◽

Decreasing Ph ◽

Targeting Ability

Novel tumor-targeting titanium dioxide (TiO2) nanoparticles modified with hyaluronic acid (HA) were developed to explore the feasibility of exploiting the pH-responsive drug release property ofTiO2and the tumor-targeting ability of HA to construct a tumor-targeting cisplatin (CDDP) delivery system (HA-TiO2) for potential neoadjuvant chemotherapy of ovarian cancer. The experimental results indicated that CDDP release from the HA-TiO2nanoparticles was significantly accelerated by decreasing pH from 7.4 to 5.0, which is of particular benefit to cancer therapy. CDDP-loaded HA-TiO2nanoparticles increased the accumulation of CDDP in A2780 ovarian cancer cells via HA-mediated endocytosis and exhibited superior anticancer activityin vitro.In vivoreal-time imaging assay revealed that HA-TiO2nanoparticles possessed preferable tumor-targeting ability which might potentially minimize the toxic side effects of CDDP in clinical application.

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