scholarly journals Fibrinolytic nanocages dissolve clots in the tumor microenvironment, improving the distribution and therapeutic efficacy of anticancer drugs

2021 ◽  
Author(s):  
Junyoung Seo ◽  
Jae Do Yoo ◽  
Minseong Kim ◽  
Gayong Shim ◽  
Yu-Kyoung Oh ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tumor Microenvironment ◽  
Anticancer Drugs ◽  
Therapeutic Efficacy ◽  
Fibrin Clot ◽  
Transport Barrier ◽  
Mouse Tumors ◽  
Mouse Melanoma Model ◽  
Melanoma Model ◽  
Fibrin Clots

AbstractFibrin, one of the components of the extracellular matrix (ECM), acts as a transport barrier within the core of tumors by constricting the blood vessels and forming clots, leading to poor intratumoral distribution of anticancer drugs. Our group previously developed a microplasmin-based thrombolytic ferritin nanocage that efficiently targets and dissolves clots without causing systemic fibrinolysis or disrupting hemostatic clots. We hypothesized that the thrombolytic nanocage-mediated degradation of fibrin clots in the tumor ECM can lead to enhanced intratumoral drug delivery, especially for nanosized anticancer drugs. Fibrin clot deposition worsens after surgery and chemotherapy, further hindering drug delivery. Moreover, the risk of venous thromboembolism (VTE) also increases. Here, we used thrombolytic nanocages with multivalent clot-targeting peptides and fibrin degradation enzymes, such as microplasmin, to dissolve fibrin in the tumor microenvironment and named them fibrinolytic nanocages (FNCs). These FNCs target tumor clots specifically and effectively. FNCs efficiently dissolve fibrin clots inside of the tumor vessels, suggesting that they can mitigate the risk of VTE in cancer patients. Coadministration of FNC and doxorubicin led to improved chemotherapeutic activity in a syngeneic mouse melanoma model. Furthermore, the FNCs increased the distribution of Doxil/doxorubicin nanoparticles within mouse tumors. These results suggest that fibrinolytic cotherapy might help improve the therapeutic efficacy of anticancer nanomedicines. Thus, microplasmin-based fibrinolytic nanocages are promising candidates for this strategy due to their hemostatic safety and ability to home in on the tumor.

Coumarin polycaprolactone polymeric nanoparticles: light and tumor microenvironment activated cocktail drug delivery

2017 ◽  
Vol 5 (9) ◽  
pp. 1734-1741 ◽  
Author(s):  
S. Karthik ◽  
Avijit Jana ◽  
M. Selvakumar ◽  
Yarra Venkatesh ◽  
Amrita Paul ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tumor Microenvironment ◽  
Anticancer Drugs ◽  
Polymeric Nanoparticles ◽  
Highly Sensitive

Highly sensitive hypoxia (H2O2)-activated photoresponsive polymeric nanoparticles for cocktail delivery of anticancer drugs doxorubicin (Dox) and chlorambucil (Cbl) were developed.

scholarly journals Capillary collagen as the physical transport barrier in drug delivery to tumor microenvironment

2015 ◽  
Vol 3 (3) ◽  
pp. e1037418 ◽  
Author(s):  
Arturas Ziemys ◽  
Kenji Yokoi ◽  
Milos Kojic
Keyword(s):  
Drug Delivery ◽  
Tumor Microenvironment ◽  
Transport Barrier

scholarly journals Immunological response in the mouse melanoma model after local hyperthermia

2008 ◽  
pp. 459-465
Author(s):  
J Kubeš ◽  
J Svoboda ◽  
J Rosina ◽  
M Starec ◽  
A Fišerová
Keyword(s):  
Tumor Microenvironment ◽  
Nk Cell ◽  
Immunological Response ◽  
B16f10 Melanoma ◽  
Mouse Melanoma Model ◽  
Melanoma Model ◽  
Release Assay ◽  
Activated Monocytes

Our study was aimed to characterize the phenotype and functional endpoints of local microwave hyperthermia (LHT, 42 °C) on tumor infiltrating and spleen leukocytes. The effectiveness of LHT applied into the tumor of B16F10 melanoma-bearing C57/BL6 mice was compared with anesthetized and non-treated animals. Subpopulations of leukocytes were analyzed using the flow cytometry, and the cytotoxic activity of splenocytes against syngeneic B16F10 melanoma and NK-sensitive YAC-1 tumor cell lines was evaluated in 51Cr-release assay. Similarly, the in vitro modification of the heat treatment was performed using healthy and melanomabearing splenocytes. We found a 40 % increase of activated monocytes (CD11b+CD69+) infiltration into the tumor microenvironment. In the spleen of experimental animals, the numbers of cytotoxic T lymphocytes (CTLs-CD3+CD8+) and NK cell (CD49b+NK1.1+) raised by 22 % and 14 %, respectively, while the NK1.1+ monocytes decreases by 37 %. This was accompanied by an enhancement of cytotoxic effector function against B16F10 and YAC-1 targets in both in vivo and in vitro conditions. These results demonstrate that LHT induces better killing of syngeneic melanoma targets. Furthermore, LHT evokes the homing of activated monocytes into the tumor microenvironment and increases the counts of NK cells and CTL in the spleen.

Magnetic liposomes for light-sensitive drug delivery and combined photothermal–chemotherapy of tumors

2019 ◽  
Vol 7 (7) ◽  
pp. 1096-1106 ◽  
Author(s):  
Song Shen ◽  
Danhuang Huang ◽  
Jin Cao ◽  
Ying Chen ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Cancer Therapy ◽  
Anticancer Drugs ◽  
Targeted Delivery ◽  
Therapeutic Efficacy

The targeted delivery of anticancer drugs for improving the therapeutic efficacy and reducing the side effects has attracted great attention in cancer therapy.

Acid- and reduction-sensitive micelles for improving the drug delivery efficacy for pancreatic cancer therapy

2018 ◽  
Vol 6 (5) ◽  
pp. 1262-1270 ◽  
Author(s):  
Pu Wang ◽  
Jinxiu Wang ◽  
Haowen Tan ◽  
Shanfan Weng ◽  
Liying Cheng ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Pancreatic Cancer ◽  
Cancer Therapy ◽  
Solid Tumors ◽  
Anticancer Drugs ◽  
Therapeutic Efficacy ◽  
Anticancer Therapy ◽  
The Poor ◽  
Pancreatic Cancer Therapy

One of the major challenges in anticancer therapy is the poor penetration of anticancer drugs into tumors, especially in solid tumors, resulting in decreased therapeutic efficacy in vivo.

scholarly journals Tumor repolarization by an advanced liposomal drug delivery system provides a potent new approach for chemo-immunotherapy

2020 ◽  
Vol 6 (36) ◽  
pp. eaba5628
Author(s):  
L. Ringgaard ◽  
F. Melander ◽  
R. Eliasen ◽  
J. R. Henriksen ◽  
R. I. Jølck ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Therapeutic Efficacy ◽  
Cytotoxic T Cells ◽  
Suppressor Cells ◽  
Immune Recognition ◽  
Liposomal Drug ◽  
Immunosuppressive Cells ◽  
Liposomal Drug Delivery

Immunosuppressive cells in the tumor microenvironment allow cancer cells to escape immune recognition and support cancer progression and dissemination. To improve therapeutic efficacy, we designed a liposomal oxaliplatin formulation (PCL8-U75) that elicits cytotoxic effects toward both cancer and immunosuppressive cells via protease-mediated, intratumoral liposome activation. The PCL8-U75 liposomes displayed superior therapeutic efficacy across all syngeneic cancer models in comparison to free-drug and liposomal controls. The PCL8-U75 depleted myeloid-derived suppressor cells and tumor-associated macrophages in the tumor microenvironment. The combination of improved cancer cell cytotoxicity and depletion of immunosuppressive populations of immune cells is attractive for combination with immune-activating therapy. Combining the PCL8-U75 liposomes with a TLR7 agonist induced immunological rejection of established tumors. This combination therapy increased intratumoral numbers of cancer antigen–specific cytotoxic T cells and Foxp3− T helper cells. These results are encouraging toward advancing liposomal drug delivery systems with anticancer and immune-modulating properties into clinical cancer therapy.

Research Progress on the Nano-Delivery Systems of Antitumor Drugs

Nano LIFE ◽  
2020 ◽  
Vol 10 (01n02) ◽  
pp. 2040006 ◽  
Author(s):  
Fan Li ◽  
Xinqing Fu ◽  
Qingqing Huo ◽  
Wantao Chen
Keyword(s):  
Drug Delivery ◽  
Anticancer Drugs ◽  
Anticancer Drug ◽  
Therapeutic Efficacy ◽  
Drug Transport ◽  
Water Solubility ◽  
Malignant Tumors ◽  
Delivery Systems ◽  
Research Progress ◽  
Anticancer Drug Delivery

To date, chemotherapy, the main treatment for malignant tumors, still fails to provide ideal therapeutic efficacy, which is deeply rooted in various physiological barriers, either temporal or spatial, to the delivering of anticancer drugs to solid tumor sites during chemotherapy. In the meantime, the therapeutic efficacy of anticancer drugs is affected by inherent cancer characteristics, drug transport, cellular uptake and other complex interactions. Recently, advances have been constantly achieved on nanoscale drug delivery systems (NDDSs) for anticancer drug delivery, driven by their excellent stability and effectiveness in improving water solubility of anticancer drugs, prolonging systemic circulation time, reducing side effects and improving anticancer effects. This paper presents an overview of the current research status and challenges in applying NDDSs to anticancer drug delivery.

scholarly journals Application of Collagen-Model Triple-Helical Peptide-Amphiphiles for CD44-Targeted Drug Delivery Systems

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Margaret W. Ndinguri ◽  
Alexander Zheleznyak ◽  
Janelle L. Lauer ◽  
Carolyn J. Anderson ◽  
Gregg B. Fields
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Stem Cell Marker ◽  
Proliferating Cells ◽  
Peptide Amphiphile ◽  
Type Iv ◽  
Helical Peptide ◽  
Mouse Melanoma Model ◽  
Melanoma Model

Cancer treatment by chemotherapy is typically accompanied by deleterious side effects, attributed to the toxic action of chemotherapeutics on proliferating cells from nontumor tissues. The cell surface proteoglycan CD44 has been recognized as a cancer stem cell marker. The present study has examined CD44 targeting as a way to selectively deliver therapeutic agents encapsulated inside colloidal delivery systems. CD44/chondroitin sulfate proteoglycan binds to a triple-helical sequence derived from type IV collagen, α1(IV)1263–1277. We have assembled a peptide-amphiphile (PA) in which α1(IV)1263–1277 was sandwiched between 4 repeats of Gly-Pro-4-hydroxyproline and conjugated to palmitic acid. The PA was incorporated into liposomes composed of DSPG, DSPC, cholesterol, and DSPE-PEG-2000 (1 : 4 : 5 : 0.5). Doxorubicin-(DOX-)loaded liposomes with and without 10% α1(IV)1263–1277 PA were found to exhibit similar stability profiles. Incubation of DOX-loaded targeted liposomes with metastatic melanoma M14#5 and M15#11 cells and BJ fibroblasts resulted in IC50 values of 9.8, 9.3, and >100 μM, respectively. Nontargeted liposomes were considerably less efficacious for M14#5 cells. In the CD44+ B16F10 mouse melanoma model, CD44-targeted liposomes reduced the tumor size to 60% of that of the untreated control, whereas nontargeted liposomes were ineffective. These results suggest that PA targeted liposomes may represent a new class of nanotechnology-based drug delivery systems.

Improved Therapeutic Efficacy of Topotecan Against A549 Lung Cancer Cells with Folate-targeted Topotecan Liposomes

2020 ◽  
Vol 21 (11) ◽  
pp. 902-909
Author(s):  
Jingxin Zhang ◽  
Weiyue Shi ◽  
Gangqiang Xue ◽  
Qiang Ma ◽  
Haixin Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Therapeutic Efficacy ◽  
Drug Delivery Systems ◽  
Lung Tumor ◽  
A549 Cells ◽  
Delivery Systems ◽  
Lung Cancer Cells

Background: Among all cancers, lung cancer has high mortality among patients in most of the countries in the world. Targeted delivery of anticancer drugs can significantly reduce the side effects and dramatically improve the effects of the treatment. Folate, a suitable ligand, can be modified to the surface of tumor-selective drug delivery systems because it can selectively bind to the folate receptor, which is highly expressed on the surface of lung tumor cells. Objective: This study aimed to construct a kind of folate-targeted topotecan liposomes for investigating their efficacy and mechanism of action in the treatment of lung cancer in preclinical models. Methods: We conjugated topotecan liposomes with folate, and the liposomes were characterized by particle size, entrapment efficiency, cytotoxicity to A549 cells and in vitro release profile. Technical evaluations were performed on lung cancer A549 cells and xenografted A549 cancer cells in female nude mice, and the pharmacokinetics of the drug were evaluated in female SD rats. Results: The folate-targeted topotecan liposomes were proven to show effectiveness in targeting lung tumors. The anti-tumor effects of these liposomes were demonstrated by the decreased tumor volume and improved therapeutic efficacy. The folate-targeted topotecan liposomes also lengthened the topotecan blood circulation time. Conclusion: The folate-targeted topotecan liposomes are effective drug delivery systems and can be easily modified with folate, enabling the targeted liposomes to deliver topotecan to lung cancer cells and kill them, which could be used as potential carriers for lung chemotherapy.

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