tumor targeting
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Author(s):  
Yvonne H. W. Derks ◽  
Sanne A. M. van Lith ◽  
Helene I. V. Amatdjais-Groenen ◽  
Lieke W. M. Wouters ◽  
Annemarie Kip ◽  
...  

Abstract  Introduction The first generation ligands for prostate-specific membrane antigen (PSMA)–targeted radio- and fluorescence-guided surgery followed by adjuvant photodynamic therapy (PDT) have already shown the potential of this approach. Here, we developed three new photosensitizer-based dual-labeled PSMA ligands by crucial modification of existing PSMA ligand backbone structures (PSMA-1007/PSMA-617) for multimodal imaging and targeted PDT of PCa. Methods Various new PSMA ligands were synthesized using solid-phase chemistry and provided with a DOTA chelator for 111In labeling and the fluorophore/photosensitizer IRDye700DX. The performance of three new dual-labeled ligands was compared with a previously published first-generation ligand (PSMA-N064) and a control ligand with an incomplete PSMA-binding motif. PSMA specificity, affinity, and PDT efficacy of these ligands were determined in LS174T-PSMA cells and control LS174T wildtype cells. Tumor targeting properties were evaluated in BALB/c nude mice with subcutaneous LS174T-PSMA and LS174T wildtype tumors using µSPECT/CT imaging, fluorescence imaging, and biodistribution studies after dissection. Results In order to synthesize the new dual-labeled ligands, we modified the PSMA peptide linker by substitution of a glutamic acid into a lysine residue, providing a handle for conjugation of multiple functional moieties. Ligand optimization showed that the new backbone structure leads to high-affinity PSMA ligands (all IC50 < 50 nM). Moreover, ligand-mediated PDT led to a PSMA-specific decrease in cell viability in vitro (P < 0.001). Linker modification significantly improved tumor targeting compared to the previously developed PSMA-N064 ligand (≥ 20 ± 3%ID/g vs 14 ± 2%ID/g, P < 0.01) and enabled specific visualization of PMSA-positive tumors using both radionuclide and fluorescence imaging in mice. Conclusion The new high-affinity dual-labeled PSMA-targeting ligands with optimized backbone compositions showed increased tumor targeting and enabled multimodal image-guided PCa surgery combined with targeted photodynamic therapy.


Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 391
Author(s):  
Hans-Georg Lerchen ◽  
Beatrix Stelte-Ludwig ◽  
Charlotte Kopitz ◽  
Melanie Heroult ◽  
Dmitry Zubov ◽  
...  

To improve tumor selectivity of cytotoxic agents, we designed VIP236, a small molecule–drug conjugate consisting of an αVβ3 integrin binder linked to a modified camptothecin payload (VIP126), which is released by the enzyme neutrophil elastase (NE) in the tumor microenvironment (TME). The tumor targeting and pharmacokinetics of VIP236 were studied in tumor-bearing mice by in vivo near-infrared imaging and by analyzing tumor and plasma samples. The efficacy of VIP236 was investigated in a panel of cancer cell lines in vitro, and in MX-1, NCI-H69, and SW480 murine xenograft models. Imaging studies with the αVβ3 binder demonstrated efficient tumor targeting. Administration of VIP126 via VIP236 resulted in a 10-fold improvement in the tumor/plasma ratio of VIP126 compared with VIP126 administered alone. Unlike SN38, VIP126 is not a substrate of P-gp and BCRP drug transporters. VIP236 presented strong cytotoxic activity in the presence of NE. VIP236 treatment resulted in tumor regressions and very good tolerability in all in vivo models tested. VIP236 represents a novel approach for delivering a potent cytotoxic agent by utilizing αVβ3 as a targeting moiety and NE in the TME to release the VIP126 payload—designed for high permeability and low efflux—directly into the tumor stroma.


2022 ◽  
Vol 11 ◽  
Author(s):  
Dan Mu ◽  
Pan He ◽  
Yesi Shi ◽  
Lai Jiang ◽  
Gang Liu

Immunotherapy can effectively activate the immune system and reshape the tumor immune microenvironment, which has been an alternative method in cancer therapy besides surgery, radiotherapy, and chemotherapy. However, the current clinical outcomes are not satisfied due to the lack of targeting of the treatment with some unexpected damages to the human body. Recently, cell membrane-based bioinspired nanoparticles for tumor immunotherapy have attracted much attention because of their superior immune regulating, drug delivery, excellent tumor targeting, and biocompatibility. Together, the article reviews the recent progress of cell membrane-based bioinspired nanoparticles for immunotherapy in cancer treatment. We also evaluate the prospect of bioinspired nanoparticles in immunotherapy for cancer. This strategy may open up new research directions for cancer therapy.


2022 ◽  
Author(s):  
Xing Li ◽  
Lingpu Zhang ◽  
Tuo Li ◽  
Shumu Li ◽  
Wenjing Wu ◽  
...  

Abstract Background: Cisplatin is the most common antitumor alkylating agent of platinum(II) (Pt(II)) in clinic, however it had many side effects. It is necessary to develop low toxicity platinum(IV) (Pt(IV)) drugs. Multi-omics was frequently used to help one understand the mechanism of a certain therapy at the molecular level. Little was known about the mechanism of Pt(IV) drugs, which may be benifical for clinical translation. Methods: We developed a Pt(IV) drug of cisplatin with two hydrophobic aliphatic chains and further encapsulated it with a drug carrier human serum albumin (HSA) to prepare Abplatin(IV). Transcriptomics, metabolomics and lipidomics were performed to clarify the mechanism of Pt(IV) drugs. T-test assay and fold change were used to find the differential substances.Results: We had further shown Abplatin(IV) had better tumor-targeting performance and greater tumor inhibtion rate than cisplatin. Lipidomics study showed that Abplatin(IV) might induce the changes of BEL-7404 cell membrane, and caused the disorder of glycerophospholipids and sphingolipids. In addition, transcriptomics and metabolomics study showed that Abplatin(IV) mainly disturbed more significant purine metabolism pathway than cisplatin.Conclusions: This research highlighted the development of Abplatin(IV) and the use of multi-omics to help one understand the mechanism of action of prodrugs and their DDS, which was the key to the clinical translation of them.


Author(s):  
Xuexia Tian ◽  
Anhua Shi ◽  
Junzi Wu

Backgroud: At present, the tumor is still the leading cause of death. Biomimetic nanocarriers for precision cancer therapy are attracting increasing attention. Nanocarriers with a good biocompatible surface could reduce the recognition and elimination of nanoparticles as foreign substances by the immune system, offer specific targeting, and improve the efficacy of precision medicine for tumors, thereby providing outstanding prospects for application in cancer therapy. In particular, cell membrane biomimetic camouflaged nanocarriers have become a research hotspot because of their excellent biocompatibility, prolonged circulation in the blood, and tumor targeting. Objective: To summarize the biological targeting mechanisms of different cell membrane-encapsulated nanocarriers in cancer therapy. In this article, the characteristics, application, and stage of progress of bionic encapsulated nanocarriers for different cell membranes are discussed, as are the field’s developmental prospects. Method: The findings on the characteristics of bionic encapsulated nanocarriers for different cell membranes and tumor treatment have been analyzed and summarized. Results: Biomimetic nanosystems based on various natural cell and hybrid cell membranes have been shown to efficiently control targeted drug delivery systems. They can reduce immune system clearance, prolong blood circulation time, and improve drug loading and targeting, thereby enhancing the diagnosis and treatment of tumors and reducing the spread of CTCs. Conclusion: :With advances in the development of biomimetic nanocarrier DDSs, novel ideas for tumor treatment and drug delivery have been developed. However, there are still some problems in biomimetic nanosystems. Therefore, it needs to be optimized through further research, from the laboratory to the clinic for the benefit of a wide range of patients.


2022 ◽  
pp. 163-188
Author(s):  
Anuranjita Kundu ◽  
Santwana Padhi ◽  
Anindita Behera ◽  
Md Saquib Hasnain ◽  
Amit Kumar Nayak
Keyword(s):  

Author(s):  
Yan-Ru Chen ◽  
Shujuan Sun ◽  
Hongwei Yin ◽  
Weijun Wang ◽  
Ran Liu ◽  
...  

By cross-catenating two DNA rings containing palindromic fragments, we demonstrate a catenane-based grid-patterned periodic DNA monolayer array ([2]GDA) capable of accumulating in tumor tissues and amenable to the delivery of anticancer drugs.


Author(s):  
Saisai Yue ◽  
Xin Zhang ◽  
Yuping Xu ◽  
Lichong Zhu ◽  
Junwei Cheng ◽  
...  

Nanomedicine based tumor targeting therapy has emerged as a promising strategy to overcome the lack of specificity of conventional chemotherapeutic agents. The “passive” targeting caused by tumor EPR effect and...


2021 ◽  
Vol 119 (1) ◽  
pp. e2109923118
Author(s):  
Mariko Sakamoto ◽  
Yoji Murata ◽  
Daisuke Tanaka ◽  
Yuka Kakuchi ◽  
Takeshi Okamoto ◽  
...  

The interaction of signal regulatory protein α (SIRPα) on macrophages with CD47 on cancer cells is thought to prevent antibody (Ab)-dependent cellular phagocytosis (ADCP) of the latter cells by the former. Blockade of the CD47-SIRPα interaction by Abs to CD47 or to SIRPα, in combination with tumor-targeting Abs such as rituximab, thus inhibits tumor formation by promoting macrophage-mediated ADCP of cancer cells. Here we show that monotherapy with a monoclonal Ab (mAb) to SIRPα that also recognizes SIRPβ1 inhibited tumor formation by bladder and mammary cancer cells in mice, with this inhibitory effect being largely dependent on macrophages. The mAb to SIRPα promoted polarization of tumor-infiltrating macrophages toward an antitumorigenic phenotype, resulting in the killing and phagocytosis of cancer cells by the macrophages. Ablation of SIRPα in mice did not prevent the inhibitory effect of the anti-SIRPα mAb on tumor formation or its promotion of the cancer cell–killing activity of macrophages, however. Moreover, knockdown of SIRPβ1 in macrophages attenuated the stimulatory effect of the anti-SIRPα mAb on the killing of cancer cells, whereas an mAb specific for SIRPβ1 mimicked the effect of the anti-SIRPα mAb. Our results thus suggest that monotherapy with Abs to SIRPα/SIRPβ1 induces antitumorigenic macrophages and thereby inhibits tumor growth and that SIRPβ1 is a potential target for cancer immunotherapy.


2021 ◽  
Vol 12 ◽  
Author(s):  
Man Zhang ◽  
Jinti Lin ◽  
Jiakang Jin ◽  
Wei Yu ◽  
Yiying Qi ◽  
...  

Gold nanorods (GNRs) are intensively explored for the application in cancer therapy, which has motivated the development of photothermal therapy (PTT) multifunctional nanoplatforms based on GNRs to cure osteosarcoma (OS). However, the major limitations include the toxicity of surface protectants of GNRs, unsatisfactory targeting therapy, and the resistant effects of photothermal-induced autophagy, so the risk of relapse and metastasis of OS increase. In the present study, the GNR multifunctional nanoplatforms were designed and synthesized to deliver transcription factor EB (TFEB)-siRNA–targeting autophagy; then, the resistance of autophagy to PTT and the pH-sensitive cell-penetrating membrane peptide (CPP) was weakened, which could improve the tumor-targeting ability of the GNR nanoplatforms and realize an efficient synergistic effect for tumor treatment. Meanwhile, it is worth noting that the GNR nanoplatform groups have anti-lung metastasis of OS. This study provides a new reference to improve the efficacy of OS clinically.


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