Self-Assembled 2D Glycoclusters for the Targeted Delivery of Theranostic Agents to Triple-Negative Breast Cancer Cells

Abstract

Triple-negative breast cancer (TNBC) is a devastating disease worldwide, for which targeted imaging and therapeutic agents remain elusive. There has been growing awareness that carbohydrates are valuable as drug candidates and targeting agents for a variety of human diseases, including cancers that overexpress carbohydrate receptors on the cell surface. Here, we develop a twodimensional (2D) glycocluster by means of simple, stepwise selfassembly for the targeted delivery of theranostic agents to TNBC cells that express mannose receptors (MRs) on the cell surface. Human serum albumin, which contains a variety of hydrophobic pockets capable of accommodating small molecules, was used to simultaneously encapsulate a mannose-based glycoprobe and a commercial photosensitizer (i.e., Ce6). The multicomponent "neoglycoprotein" formed was used to self-assemble with 2D MnO 2 , producing 2D glycoclusters, which could be selectively internalized by a TNBC cell line (MDA-MB-231) as facilitated by binding to the transmembrane MR. The intracellular degradation of the 2D MnO 2 backbone by biothiols then released Ce6 for cell imaging and, subsequently, photodynamic therapy. This study provides insights into the development of carbohydrate-based materials for targeted, stimuli-responsive theranostics of TNBC.

Mannose receptor in differentgrades of breast cancer and ER, BR and Herneu-2 panel

“…The present study revealed that the results of immunhistochemistry (IHC) panel including estrogen ER ,progesterone PR andher2n receptor, in each sub group both positive and negative receptors had significant correlation in serum mannose receptor compared with control, this result is agreed withPirasandXi-Le Hu . (3,11) although they were used histological laboratory technique. Jing Fang showed interest about the importance of lower traumatic detection and diagnosis method because most of the diagnosis methods failed reflectance the heterogeneity of breast cancer.…”

“…Most of cancer cases enrolled in the present study are categorized within Grade II and III including 42(68.9%) and 19(31.1%) respectively.According to the results of present study, blood levels of MR markers showing significant correlation between GII,GIII groups and control as shown in table (2) receptors (ER) detected by Immunohistochmestryachived on paraffin embedded blocks of breast cancer for the patients including in the present study showing 47(77%) ER positive while 14 (23%) ER negative.MR blood levels by ELISA showing statistically significant correlation between their level in patients with both ER positive and negative in comparison with control as shown in table( 3) Regarding progesterone receptor (PR) detected by IHC 40(65.6%) of patients have PR positive while 21 (34.4%) have PR negative.…”

“…(2) Mannose receptor (MR), CD206, is about 175 kDa in size, an endocytotic membrane protein with multiple carbohydrate recognition domains, originally termed the macrophage mannose receptor,overexpresses MR on the cell surface, mediating active endocytosis of glycoconjugates. (3) Protein glycosylation is one of the most frequent and well-known posttranslational modifications in protein, which plays important roles in physiopathological processes. Altered glycosylation on the cell surface of cancer cells is hall mark of tumorigenesis, tumor progression and metastasis.…”

Current Photoactive Molecules for Targeted Therapy of Triple-Negative Breast Cancer

“…Regarding the PDT mechanisms, it was observed that, at a concentration of 5.0 μM and a total light dose of 1.96 J cm −2 , the cells treated with CBTN, InCBTN, MePheo and InCBX presented morphological apoptosis characteristics, such as nuclear fragments and chromatin condensation; additionally, there was no indication that necrotic or autophagic pathways were responsible for cell death mechanisms, thus apoptosis seems to be the mechanism behind the photoactivation of these delivery systems by PDT [83]. He and co-workers [84] reported the synthesis of a two-dimensional glycocluster, based on 2D MnO2, for the targeted delivery of theranostic agents (Figure 12). The synthesis involved the formation of the mannose-based glycoprobe through click conjugation between a PEG-linked azido-mannoside and an alkynyldicyanomethylene-4H-pyran dye.…”

“…Several classes of molecules, such as tetrapyrrolic macrocycles and analogues, including porphyrins [64][65][66][67][68][69][70][71], phthalocyanines [72,73], chlorins [22,23,[74][75][76][77][78][79][80][81][82][83][84][85][86], the prodrug 5-aminolevulinic acid (5-ALA) [87][88][89] and other dyes, such as adequately conjugated indocyanine green [90][91][92][93][94], have been explored as PS in TNBC targeted therapy. Chlorins and their analogues are very interesting molecules; besides their natural source and/or semi-synthetic preparation, these molecules exhibit good absorption in the therapeutic window (600-800 nm), which is an important feature for a good candidate for clinical PDT, due to the better light penetration in tissues (≈1-2 cm), which overcomes the light penetration limitation when other photosensitizers are used, such as porphyrins [48,49,95].…”