Construction and antitumor properties of a targeted nano-drug carrier system responsive to the tumor microenvironment

Han, Wei; Ke, Junfeng; Guo, Feng; Meng, Fanwei; Li, Hui; Wang, Liping

doi:10.1016/j.ijpharm.2021.121066

Cited by 8 publications

(4 citation statements)

References 57 publications

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“…In this study, dual-modality imaging with the albumin nanosystem in vivo is used to guide the radiation of the verified lesion site and identify the optimal light time. In contrast to normal tissues, tumor present with abundant new blood vessels, inadequate structural stability, impaired lymphatic drainage and heightened permeability [ 40 ]. Thus, the nanoparticles could retention in tumor tissues owing to the EPR effect, thereby significantly increasing the delivery efficacy [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

Albumin-based nanosystem for dual-modality imaging-guided chem-phototherapy against immune-cold triple-negative breast cancer

Peng,

Zeng,

Cai

et al. 2023

Regenerative Biomaterials

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Triple-negative breast cancer is a highly aggressive and metastatic tumor; diagnosing it in the early stages is still difficult, and the prognosis for conventional radio-chemotherapy and immunotreatment is not promising due to cancer’s immunosuppressive microenvironment. The utilization of protein-based nanosystem has proven to be effective in delivering agents with limited adverse effects, yet the combination of diagnosis and treatment remains a difficult challenge. This research took advantage of natural albumin and organic molecules to construct a self-assemble core-shell nanostructure combining with superparamagnetic iron oxide nanocrystals and heptamethine cyanine dye IR780 through non-covalent interactions. This nanocomposite successfully decreased the transverse relaxation time of the magnetic resonance hydrogen nucleus, resulting in outstanding T2 imaging, as well as emitting near-infrared II fluorescence, thereby the resulting dual-modality imaging tool was applied to improve diagnostic competency. It is noteworthy that the nanocomposites exhibited impressive enzyme-like catalytic and photothermal capabilities, resulting in a successful activation of the immune system to efficiently suppress distant metastatic lesions in vivo. Consequently, this nanodrug-based therapy could be an advantageous asset in reinforcing the immune system and hindering the growth and reappearance of the immune-cold breast cancer.

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Section: Resultsmentioning

confidence: 99%

Albumin-based nanosystem for dual-modality imaging-guided chem-phototherapy against immune-cold triple-negative breast cancer

Peng,

Zeng,

Cai

et al. 2023

Regenerative Biomaterials

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“…Another approach to promoting the full potential and minimizing the systemic toxicity of IBR is to target these small-molecule kinase modulators to the tumor-infiltrating T cells and tumor immune microenvironment. , Sialic acid-binding immunoglobulin-like lectins (Siglecs) were previously reported to be expressed only in a minority of peripheral normal T cells . However, Siglec-E (the murine functional paralog of Siglec-9) was recently found to be upregulated in tumor-infiltrating T cells in melanoma, non-small cell lung cancer, and colorectal cancer mouse models .…”

Section: Introductionmentioning

confidence: 99%

Targeting Ibrutinib to Tumor-Infiltrating T Cells with a Sialic Acid Conjugate-Modified Phospholipid Complex for Improved Tumor Immunotherapy

et al. 2022

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Immune checkpoint blockade (ICB) treatment for the clinical therapy of numerous malignancies has attracted widespread attention in recent years. Despite being a promising treatment option, developing complementary strategies to enhance the proportion of patients benefiting from ICB therapy remains a formidable challenge because of the complexity of the tumor microenvironment. Ibrutinib (IBR), a covalent inhibitor of Bruton's tyrosine kinase (BTK), has been approved as a clinical therapy for numerous B-cell malignancies. IBR also irreversibly inhibits interleukin-2 inducible T cell kinase (ITK), an essential enzyme in Th2-polarized T cells that participates in tumor immunosuppression. Ablation of ITK by IBR can elicit Th1-dominant antitumor immune responses and potentially enhance the efficacy of ICB therapy in solid tumors. However, its poor solubility and rapid clearance in vivo restrict T cell targetability and tumor accumulation by IBR. A sialic acid derivative-modified nanocomplex (SA-GA-OCT@PC) has been reported to improve the efficacy of IBR-mediated combination immunotherapy in solid tumors. In vitro and in vivo experiments showed that SA-GA-OCT@PC effectively accumulated in tumor-infiltrating T cells mediated by Siglec-E and induced Th1-dominant antitumor immune responses.

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“…To overcome resistance, higher doses of Gem are required, which lead to severe systemic toxicity [ 12 , 13 ]. The control of the drug release site and time could improve drug efficacy, with lower doses and toxicity [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…Through such a DDS, it is possible to selectively release the drug in the acidic tumor microenvironment while maintaining the drug’s stability within the DDSs in normal tissue [ 16 ]. Several examples of pH-responsive DDSs have been proposed over time, including chitosan-coated mesoporous silica nanoparticles, liposomes, polymeric micelles, and nanospheres [ 5 , 14 , 15 , 17 , 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Microfluidic-Assisted Preparation of Targeted pH-Responsive Polymeric Micelles Improves Gemcitabine Effectiveness in PDAC: In Vitro Insights

Iacobazzi

Arduino

Fonte

et al. 2021

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) represents a great challenge to the successful delivery of the anticancer drugs. The intrinsic characteristics of the PDAC microenvironment and drugs resistance make it suitable for therapeutic approaches with stimulus-responsive drug delivery systems (DDSs), such as pH, within the tumor microenvironment (TME). Moreover, the high expression of uPAR in PDAC can be exploited for a drug receptor-mediated active targeting strategy. Here, a pH-responsive and uPAR-targeted Gemcitabine (Gem) DDS, consisting of polymeric micelles (Gem@TpHResMic), was formulated by microfluidic technique to obtain a preparation characterized by a narrow size distribution, good colloidal stability, and high drug-encapsulation efficiency (EE%). The Gem@TpHResMic was able to perform a controlled Gem release in an acidic environment and to selectively target uPAR-expressing tumor cells. The Gem@TpHResMic displayed relevant cellular internalization and greater antitumor properties than free Gem in 2D and 3D models of pancreatic cancer, by generating massive damage to DNA, in terms of H2AX phosphorylation and apoptosis induction. Further investigation into the physiological model of PDAC, obtained by a co-culture of tumor spheroids and cancer-associated fibroblast (CAF), highlighted that the micellar system enhanced the antitumor potential of Gem, and was demonstrated to overcome the TME-dependent drug resistance. In vivo investigation is warranted to consider this new DDS as a new approach to overcome drug resistance in PDAC.

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Construction and antitumor properties of a targeted nano-drug carrier system responsive to the tumor microenvironment

Cited by 8 publications

References 57 publications

Albumin-based nanosystem for dual-modality imaging-guided chem-phototherapy against immune-cold triple-negative breast cancer

Albumin-based nanosystem for dual-modality imaging-guided chem-phototherapy against immune-cold triple-negative breast cancer

Targeting Ibrutinib to Tumor-Infiltrating T Cells with a Sialic Acid Conjugate-Modified Phospholipid Complex for Improved Tumor Immunotherapy

Microfluidic-Assisted Preparation of Targeted pH-Responsive Polymeric Micelles Improves Gemcitabine Effectiveness in PDAC: In Vitro Insights

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