循环肿瘤细胞簇促进血行转移的分子机制研究

肿瘤转移是导致肿瘤患者死亡的重要原因,一旦发生转移,癌症将会变得更加难以治疗,许多研究已经观察到转移患者循环系统中存在循环肿瘤细胞(circulating tumor cells,CTCs),CTCs的检测可以用于预测临床结果,并可用于监测抗转移药物干预措施的疗效。CTCs在血行转移的过程中,偶尔会以团簇的形式出现,这些聚集的肿瘤细胞团与单个CTC相比,具有更高的转移特性,循环肿瘤细胞簇(circulating tumor cells clusters,CTC clusters)捕获技术的发展为肿瘤转移提供了新见解。该文讨论了CTC clusters形成的分子机制及其在肿瘤血行转移中的作用,并评价了其在治疗中作为生物标记物和治疗靶标的临床价值。     

Lipid–polymer nanoparticles encapsulating curcumin for modulating the vascular deposition of breast cancer cells

Vascular adhesion and endothelial transmigration are critical steps in the establishment of distant metastasis by circulating tumor cells (CTCs). Also, vascular inflammation plays a pivotal role in steering CTCs out of the blood stream. Here, long circulating lipid–polymer nanoparticles encapsulating curcumin (NANOCurc) are proposed for modulating the vascular deposition of CTCs. Upon treatment with NANOCurc, the adhesion propensity of highly metastatic breast cancer cells (MDA-MB-231) onto TNF-α stimulated endothelial cells (HUVECs) reduces by ~ 70%, in a capillary flow. Remarkably, the CTCs vascular deposition already reduces up to ~ 50% by treating solely the inflamed HUVECs. The CTCs arrest is mediated by the interaction between ICAM-1 on HUVECs and MUC-1 on cancer cells, and moderate doses of curcumin down-regulate the expression of both molecules. This suggests that NANOCurc could prevent metastasis and limit the progression of the disease by modulating vascular inflammation and impairing the CTCs arrest.From the Clinical EditorIn this novel study, lipid nanoparticles encapsulating curcumin were able to prevent metastasis formation and limited the progression of the disease by modulating vascular inflammation and impairing the circulating tumor cells' arrest as a result of down-regulation of ICAM1 and MUC1 in a highly metastatic breast cancer cell line model.     

Nanoplateletsomes restrain metastatic tumor formation through decoy and active targeting in a preclinical mouse model

Platelets buoy up cancer metastasis via arresting cancer cells, enhancing their adhesion, and facilitating their extravasation through the vasculature. When deprived of intracellular and granular contents, platelet decoys could prevent metastatic tumor formation. Inspired by these, we developed nanoplatesomes by fusing platelet membranes with lipid membranes (P-Lipo) to restrain metastatic tumor formation more efficiently. It was shown nanoplateletsomes bound with circulating tumor cells (CTC) efficiently, interfered with CTC arrest by vessel endothelial cells, CTC extravasation through endothelial layers, and epithelial-mesenchymal transition of tumor cells as nanodecoys. More importantly, in the mouse breast tumor metastasis model, nanoplateletsomes could decrease CTC survival in the blood and counteract metastatic tumor growth efficiently by inhibiting the inflammation and suppressing CTC escape. Therefore, nanoplatelesomes might usher in a new avenue to suppress lung metastasis.     

Cancer stemness contributes to cluster formation of colon cancer cells and high metastatic potentials

The ability of cancer cells to form clusters is a characteristic feature in the development of metastatic tumours with drug resistance. Several studies demonstrated that clusters of circulating tumour cells (CTCs) have a greater metastatic potential to establish new tumours at secondary sites than single CTCs. However, the mechanism of cluster formation is not well understood. In this study, we investigated whether cancer stemness would contribute to cluster formation. We used a tumour sphere culture method to enrich cancer stem cells (CSCs) from colon cancer cells and found that during the second generation of sphere culture, clusters (between 3 and 5 cells) formed within the first 24 hours, whereas the rest remained as single cells. The clusters were analysed for stemness and metastatic potential, including gene expressions for cancer stemness (CD133 and Lgr5), epithelial-mesenchymal transition (E-cadherin and TGF-β 1-3) and hypoxia-induced factors (HIF-1α and HIF-2α). The results showed that the clusters expressed higher levels of these genes and colon CSC surface markers (including CD24, CD44 and CD133) than the single cells. Among these markers, CD24 seemed the major contributor linking the cells into the clusters. These clusters also showed a stronger ability to both form colonies and migrate. Our data collectively suggest that colon cancer stemness contributes to cluster formation and that clustered cells exhibit a great metastatic potential. Our study thus provides a method to study the CTC clusters and derive insight into oncogenesis and metastasis.     

All-stage targeted therapy for the brain metastasis from triple-negative breast cancer

Brain metastasis is a common and serious complication of breast cancer, which is commonly associated with poor survival and prognosis. In particular, the treatment of brain metastasis from triple-negative breast cancer (BM-TNBC) has to face the distinct therapeutic challenges from tumor heterogeneity, circulating tumor cells (CTCs), blood–brain barrier (BBB) and blood–tumor barrier (BTB), which is in unmet clinical needs. Herein, combining with the advantages of synthetic and natural targeting moieties, we develop a “Y-shaped” peptide pVAP-decorated platelet-hybrid liposome drug delivery system to address the all-stage targeted drug delivery for the whole progression of BM-TNBC. Inherited from the activated platelet, the hybrid liposomes still retain the native affinity toward CTCs. Further, the peptide-mediated targeting to breast cancer cells and transport across BBB/BTB are demonstrated in vitro and in vivo. The resultant delivery platform significantly improves the drug accumulation both in orthotopic breast tumors and brain metastatic lesions, and eventually exhibits an outperformance in the inhibition of BM-TNBC compared with the free drug. Overall, this work provides a promising prospect for the comprehensive treatment of BM-TNBC, which could be generalized to other cell types or used in imaging platforms in the future.     

Fucoidan-functionalized activated platelet-hitchhiking micelles simultaneously track tumor cells and remodel the immunosuppressive microenvironment for efficient metastatic cancer treatment

Tumor metastasis is responsible for most mortality in cancer patients, and remains a challenge in clinical cancer treatment. Platelets can be recruited and activated by tumor cells, then adhere to circulating tumor cells (CTCs) and assist tumor cells extravasate in distant organs. Therefore, nanoparticles specially hitchhiking on activated platelets are considered to have excellent targeting ability for primary tumor, CTCs and metastasis in distant organs. However, the activated tumor-homing platelets will release transforming growth factor-β (TGF-β), which promotes tumor metastasis and forms immunosuppressive microenvironment. Therefore, a multitalent strategy is needed to balance the accurate tumor tracking and alleviate the immunosuppressive signals. In this study, a fucoidan-functionalized micelle (FD/DOX) was constructed, which could efficiently adhere to activated platelets through P-selectin. Compared with the micelle without P-selectin targeting effect, FD/DOX had increased distribution in both tumor tissue and metastasis niche, and exhibited excellent anti-tumor and anti-metastasis efficacy on 4T1 spontaneous metastasis model. In addition, due to the contribution of fucoidan, FD/DOX treatment was confirmed to inhibit the expression of TGF-β, thereby stimulating anti-tumor immune response and reversing the immunosuppressive microenvironment. The fucoidan-functionalized activated platelets-hitchhiking micelle was promising for the metastatic cancer treatment.     

Overview of current standpoints in profiling of circulating tumor cells

The goal of this review is summarizing current technologies developed as the in vitro prognostic/diagnostic systems that can rapidly separate and detect circulating tumor cells (CTCs) from cancer patient’s blood (1–10 CTCs of 1 billion red blood cells) by labeled and non-labeled method. The review is focused on three major areas of CTC research (1) Summary of previous research on capturing of CTCs, (2) New development of the in vitro prognostic diagnosis system of cancer that is capable of rapid separation of CTCs, (3) Future direction on development of new technologies for CTC profiling. Current CTC researches have helped on identifying patients who may benefit from chemotherapy before treatment, patients who may benefit from continued chemotherapy, and leading to clinical development of CTC-guided chemotherapy strategies. We analyze the feasibility of clinical application of these current CTC research for the ultimate goal of increasing the survivability of cancer patient. The biomolecular assays of viable CTCs from cancer patient may elucidate the mechanism of metastasis and tumor initiating cells and also may have high impact on the development of personalized medicine to overcome the incurable diseases.     

Cancer-specific calcium nanoregulator suppressing the generation and circulation of circulating tumor cell clusters for enhanced anti-metastasis combinational chemotherapy

Tumor metastasis is responsible for chemotherapeutic failure and cancer-related death. Moreover, circulating tumor cell (CTC) clusters play a pivotal role in tumor metastasis. Herein, we develop cancer-specific calcium nanoregulators to suppress the generation and circulation of CTC clusters by cancer membrane-coated digoxin (DIG) and doxorubicin (DOX) co-encapsulated PLGA nanoparticles (CPDDs). CPDDs could precisely target the homologous primary tumor cells and CTC clusters in blood and lymphatic circulation. Intriguingly, CPDDs induce the accumulation of intracellular Ca²⁺ by inhibiting Na⁺/K⁺-ATPase, which help restrain cell–cell junctions to disaggregate CTC clusters. Meanwhile, CPDDs suppress the epithelial–mesenchymal transition (EMT) process, resulting in inhibiting tumor cells escape from the primary site. Moreover, the combination of DOX and DIG at a mass ratio of 5:1 synergistically induces the apoptosis of tumor cells. In vitro and in vivo results demonstrate that CPDDs not only effectively inhibit the generation and circulation of CTC clusters, but also precisely target and eliminate primary tumors. Our findings present a novel approach for anti-metastasis combinational chemotherapy.     

一种基于体内CTC捕获的CellCollector®技术对乳腺癌患者分层的价值

目的　探讨基于CellCollector®技术捕获的循环肿瘤细胞（CTC）用于筛选转移风险较高的乳腺癌患者的可能性。方法　入组60例原发性乳腺癌患者为乳腺癌组,其中Ⅰ期16例、Ⅱ期29例、Ⅲ期11例、Ⅳ期4例。通过CellCollector®进行至少1次外周血CTC检测,并随访4～19个月。同时入组10例健康女性志愿者作为对照组,仅进行1次CTC检测。分析不同年龄、绝经情况、TNM分期、分子分型、Ki-67表达程度患者CTC阳性率的差异。结果　乳腺癌组基线CTC检出率为73.33%;Ⅰ~Ⅳ期检出率分别为43.75%、82.76%、81.82%和100%,不同临床分期下CTC检出率差异有统计学意义。不同年龄、是否绝经、不同分子分型及Ki-67表达程度患者CTC检出率差异均无统计学意义。24例行2次CTC检测。4例疾病进展患者中,1例CTC数目增多;20例无疾病进展患者中,3例CTC数目增加。CTC数目动态变化与疾病进展不存在相关性。结论　CellCollector®体内CTC检测技术在非转移性乳腺癌中检出率较高,为CTC筛选转移风险较高的乳腺癌患者提供了可能。     

Cancer-specific calcium nanoregulator suppressing the generation and circulation of circulating tumor cell clusters for enhanced anti-metastasis combinational chemotherapy

Tumor metastasis is responsible for chemotherapeutic failure and cancer-related death. Moreover, circulating tumor cell (CTC) clusters play a pivotal role in tumor metastasis. Herein, we develop cancer-specific calcium nanoregulators to suppress the generation and circulation of CTC clusters by cancer membrane-coated digoxin (DIG) and doxorubicin (DOX) co-encapsulated PLGA nanoparticles (CPDDs). CPDDs could precisely target the homologous primary tumor cells and CTC clusters in blood and lymphatic circulation. Intriguingly, CPDDs induce the accumulation of intracellular Ca²⁺ by inhibiting Na⁺/K⁺-ATPase, which help restrain cell–cell junctions to disaggregate CTC clusters. Meanwhile, CPDDs suppress the epithelial–mesenchymal transition (EMT) process, resulting in inhibiting tumor cells escape from the primary site. Moreover, the combination of DOX and DIG at a mass ratio of 5:1 synergistically induces the apoptosis of tumor cells. In vitro and in vivo results demonstrate that CPDDs not only effectively inhibit the generation and circulation of CTC clusters, but also precisely target and eliminate primary tumors. Our findings present a novel approach for anti-metastasis combinational chemotherapy.KEY WORDS: Cell–cell junctions, Digoxin, Doxorubicin, Homologous targeting, Circulating tumor cell clusters, Epithelial–mesenchymal transition, Breast cancer, Lung metastasis     

吖啶橙荧光染色法在循环肿瘤细胞筛查中的应用

目的：应用吖啶橙荧光（AO-F）染色法搭建循环肿瘤细胞（CTCs）筛选平台,以及该方法在肾癌患者外周血中的应用初探。方法：传代培养肾肿瘤细胞,AO-F染色后随机计数5个视野下AO-F+细胞占肿瘤细胞的比例,评估AO-F染料对肿瘤细胞的敏感性;清晨空腹抽取10例健康体检者（对照组）外周血,红细胞裂解后富集单个核细胞,与一定数量的肿瘤细胞混合,建立肾癌外周血CTCs模型,AO-F染色后计算肿瘤细胞回收率,评估本方法特异性及稳定性;选取27例转移性肾癌患者作为实验组,采用AO-F法检测两组（对照组、实验组）外周血AO-F+细胞的检出率并分析检出率与患者临床参数之间的关系。结果: 平均每个视野下AO-F+细胞占肿瘤细胞的比例为93%±3%。含500、200、100、50个细胞的悬液组肿瘤细胞回收率（%）分别为：10.2±3.8、9.2±2.3、10.8±2.6、10.5±1.9,组间差异无统计学意义（F=1.001,P＞0.05）。含10个细胞的悬液组偶然可检测到AO-F+细胞。对照组无一例阳性,实验组9例检测到AO-F+细胞,检出率为33.33%;检出率与年龄、性别、肿瘤大小、病理类型、Furhman分级、转移部位及带瘤状态均没有统计学差异（P＞0.05）。结论：本研究证实了AO-F染色法筛查外周血CTCs切实可行,并具有高度的特异性和可重复性。对早期预测肾癌复发转移有一定参考价值。     

广西地区复发转移乳腺癌临床病理因素及激素受体状况的相关研究

目的 探讨广西地区复发转移乳腺癌临床病理因素、激素受体状况及二者相关性.方法 应用免疫组化方法,检测接受根治手术的女性乳腺癌患者100例中的ER、PR、CerbB-2、表达情况.结果 发病年龄、肿瘤大小、腋淋巴结转移状况、pTNM分期、ER的表达与乳腺癌患者根治手术后累积复发转移率有关,多因素分析显示最终进入COX模型的仅有ER.结论 乳腺癌术后复发转移与发病年龄、肿瘤大小、腋淋巴结转移状况、pTNM分期有关.ER可作为乳腺癌术后复发转移的预测指标.     

Natural exosome-like nanovesicles from edible tea flowers suppress metastatic breast cancer via ROS generation and microbiota modulation

Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer, their inefficient therapeutic outcomes, serious adverse effects, and high cost of mass production remain crucial challenges. Herein, we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers (TFENs). These nanovehicles had desirable particle sizes (131 nm), exosome-like morphology, and negative zeta potentials. Furthermore, TFENs were found to contain large amounts of polyphenols, flavonoids, functional proteins, and lipids. Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species (ROS) amplification. The increased intracellular ROS amounts could not only trigger mitochondrial damage, but also arrest cell cycle, resulting in the in vitro anti-proliferation, anti-migration, and anti-invasion activities against breast cancer cells. Further mice investigations demonstrated that TFENs after intravenous (i.v.) injection or oral administration could accumulate in breast tumors and lung metastatic sites, inhibit the growth and metastasis of breast cancer, and modulate gut microbiota. This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v. and oral routes.     

Comparison of select cancer biomarkers in human circulating and bulk tumor cells using magnetic nanoparticles and a miniaturized micro-NMR system

Circulating tumor cells (CTC) harvested from peripheral blood have received significant interest as sources for serial sampling to gauge treatment efficacy. Nanotechnology and microfluidic based approaches are emerging to facilitate such analyses. While of considerable clinical importance, there is little information on how similar or different CTCs are from their shedding bulk tumors. In this clinical study, paired tumor fine needle aspirate and peripheral blood samples were obtained from cancer patients during image-guided biopsy. Using targeted magnetic nanoparticles and a point-of-care micro-NMR system, we compared selected biomarkers (EpCAM, EGFR, HER-2 and vimentin) in both CTC and fine needle biopsies of solid epithelial cancers. We show a weak correlation between each paired sample, suggesting that use of CTC as “liquid biopsies” and proxies to metastatic solid lesions could be misleading.From the Clinical EditorIn this clinical study, paired tumor fine needle aspirate and peripheral blood samples were obtained from patients with solid epithelial cancers during image-guided biopsy. Using targeted magnetic nanoparticles and a point-of-care micro-NMR system, the authors compared selected biomarkers in both circulating tumor cells (CTC) and fine needle biopsies, demonstrating a weak correlation between each paired sample, suggesting that use of CTC could be misleading in this context.     

A drug-delivering-drug strategy for combined treatment of metastatic breast cancer

Treatment of metastatic cancer continues to be a huge challenge worldwide. Notably, drug nanocrystals (Ns) in nanosuspensions clearly belong to a type of nanoparticle. Therefore, a question arose as to whether these drug particles can also be applied as carriers for drug delivery. Here, we design a novel paclitaxel (PTX) nanocrystal stabilized with complexes of matrix metalloproteinase (MMP)-sensitive β-casein/marimastat (MATT) for co-delivering MATT and PTX and combined therapy of metastatic breast cancer. The prepared Ns (200?nm) with a drug-loading of >50% were potent in treatment of metastatic cancer, which markedly inhibited MMP expression and activity and greatly blocked the lung metastasis and angiogenesis. In conclusion, employing protein–drug complexes as stabilizers, Ns with dual payloads are developed and are a promising strategy for co-delivery. Furthermore, the developed Ns can target the tumor microenvironment and cancer cells and, as a result, enable efficient treatment for breast metastatic cancer.     

Detection of circulating tumor cells in breast cancer with a refined immunomagnetic nanoparticle enriched assay and nested-RT-PCR

Early detection of circulation tumor cells (CTCs) in breast cancer patients has great clinical relevance. Currently, immunomagnetic microparticles enriched assays require Fe₃O₄ inner cores, making it difficult to improve sensitivity. In this study, we prepared magnetic nanoparticles with carbon-coated pure iron (Fe@C) acted as the core, Conjugating with EpCAM monoclonal antibody for immunomagnetic nanoparticles(IMPs). IMPs were used in conjunction with immunocytochemistry (ICC) to develop a refined immunomagnetic nanoparticles enriched assay (IMPEA) for detection of circulating tumor cells (CTCs) in breast cancer patients. Compared with nested RT-PCR, this method achieved the same sensitivity, but with a significantly reduced false-positive rate. This method will help find hidden micrometastases, establish clinical stage, and guide individual treatment post-surgery, suggesting potentially significant value in the clinic.From the Clinical EditorThis team of investigators prepared magnetic nanoparticles with carbon-coated pure iron as core and conjugated them with EpCAM monoclonal antibody to form immunomagnetic nanoparticles for circulating tumor cell (CTC) detection. Compared with nested RT-PCR, this method achieved the same sensitivity, but with a significantly reduced false-positive rate, paving the way to the development of a tool that enables enhanced detection of micrometastases and post-surgical treatment monitoring.     

T7 RNA聚合酶催化荧光扩增技术检测结直肠癌患者外周血肿瘤细胞的临床意义

目的:探讨T7 RNA聚合酶催化荧光扩增技术检测结直肠癌患者术前外周血中循环肿瘤细胞的临床意义.方法:以CEA作为循环肿瘤细胞标志物,采用T7 RNA聚合酶催化的荧光扩增技术,术前检测68例结直肠癌(结直肠癌组)及30例健康人(对照组)的外周血循环肿瘤细胞,并分析结直肠癌患者术前外周血中循环肿瘤细胞的检出率与临床病理特征的关系.结果:结直肠癌组总的循环肿瘤细胞检出率75.00%(51/68),57例无远处转移和11例有远处转移者检出率分别为70.20%(40/57)和100.00%(11/11).循环肿瘤细胞在结直肠癌组 Dukes A、B、C、D期检出率分别为36.36%(4/11)、68.42%(13/19)、85.19%(23/27)和100.00%(11/11),Dukes C D期检出率明显高于Dukes A B期(P<0.01).淋巴结转移者检出率为86.84%,而无转移者为60.00%,两者比较差异具有显著性统计学意义(P<0.05).对照组出现1例假阳性,此方法的特异性为97%.结论:采用T7 RNA聚合酶催化荧光扩增技术检测结直肠癌患者外周血循环肿瘤细胞检出率较高,其术前检出率与肿瘤分期和淋巴结转移密切相关,对结直肠癌早期诊断及判断预后具有重要意义.     

Nanoparticles (NPs)-mediated lncBCMA silencing to promote eEF1A1 ubiquitination and suppress breast cancer growth and metastasis

Long non-coding RNAs (lncRNAs) play an important role in cancer metastasis. Exploring metastasis-associated lncRNAs and developing effective strategy for targeted regulation of lncRNA function in vivo are of utmost importance for the treatment of metastatic cancer, which however remains a big challenge. Herein, we identified a new functional lncRNA (denoted lncBCMA), which could stabilize the expression of eukaryotic translation elongation factor 1A1 (eEF1A1) via antagonizing its ubiquitination to promote triple-negative breast cancer (TNBC) growth and metastasis. Based on this regulatory mechanism, an endosomal pH-responsive nanoparticle (NP) platform was engineered for systemic lncBCMA siRNA (siBCMA) delivery. This NPs-mediated siBCMA delivery could effectively silence lncBCMA expression and promote eEF1A1 ubiquitination, thereby leading to a significant inhibition of TNBC tumor growth and metastasis. These findings show that lncBCMA could be used as a potential biomarker to predict the prognosis of TNBC patients and NPs-mediated lncBCMA silencing could be an effective strategy for metastatic TNBC treatment.     

High salt diet may promote progression of breast tumor through eliciting immune response

ObjectiveDietary patterns are believed to regulate tumor progression by altering the tumor microenvironment. Of note, a high salt diet is a risk factor for various diseases. However, the role of high salt intake in the progression of cancers remains unknown.MethodsWe constructed an in vivo high salt diet model in MMTV-PyVT mice with spontaneous tumor-forming properties to explore the role of a high salt diet in the progression of breast cancer as well as the modulation of the tumor microenvironment. Also, in vitro experiments were performed to understand the mechanism.ResultsHigh salt diet accelerated the development (P < 0.05) and lung metastasis (P < 0.05) of breast cancer in MMTV-PyVT mice, compared to the normal diet model. Moreover, higher frequency of Th17 cells in circulation, tumor tissue and draining lymph node tissue were observed in the high salt diet model (P < 0.05 for all). In vitro, co-culture with Th17 cells facilitated the proliferation, migration and invasion of MCF-7 human breast cancer cells, while these enhanced aggressive behaviors could be reversed by application of 1,25-vitamin D₃ which could inhibit the differentiation of Th17 cells (P < 0.001 for all). In vitro, co-culture with Th17 cells activated MAPK signaling in MCF-7 cells (P < 0.001 for all). Consistently, activated MAPK/ERK signaling was observed by immunohistochemistry in breast cancer cell nodes in the high salt diet model (P < 0.05 for all). Mechanistically, higher level of IL-17F could be detected in breast tumors and serum from the high salt diet model through qRT-PCR and ELISA (P < 0.05 for all). IL-17F treatment facilitated the proliferation, migration and invasion of MCF-7 human breast cancer cells and activated MAPK/ERK signaling in MCF-7 cells (P < 0.001 for all). Moreover, the tumor-promoting function induced by Th17 cells and IL-17F could be inhibited by the administration of ERK inhibitor (sch772894) (P < 0.001 for all). Lastly, high concentration NaCl-induced Th17 cells promoted the proliferation, migration and invasion of MCF-7 human breast cancer cells and activated MAPK/ERK signaling in MCF-7 cells which could be inhibited by neutralizing anti-IL-17F (P < 0.001 for all).ConclusionHigh salt intake accelerates the growth of breast cancer and facilitates lung metastasis, as well as increases the level of Th17 cells. Increased Th17 cells might promote the growth of breast cancer via the secretion of IL-17F to activate the MAPK signaling pathway in breast cancer cells.     

A rationally designed photo-chemo core-shell nanomedicine for inhibiting the migration of metastatic breast cancer cells followed by photodynamic killing

A multifunctional core-shell nanomedicine capable of inhibiting the migratory capacity of metastatic cancer cells followed by imparting cytotoxic stress by photodynamic action is reported. Based on in silico design, we have developed a core-shell nanomedicine comprising of ~ 80 nm size poly(lactic-co-glycolic acid) (PLGA) nano-core encapsulating photosensitizer, m-tetra(hydroxyphenyl)chlorin (mTHPC), and ~ 20 nm size albumin nano-shell encapsulating tyrosine kinase inhibitor, Dasatinib, which impair cancer migration. This system was prepared by a sequential process involving electrospray of polymer core and coacervation of protein shell. Cell studies using metastatic breast cancer cells demonstrated disruption of Src kinase involved in the cancer migration by albumin–dasatinib nano-shell and generation of photoactivated oxidative stress by mTHPC-PLGA nano-core. This unique combinatorial photo-chemo nanotherapy resulted synergistic cytotoxicity in ~ 99% of the motility-impaired metastatic cells. This approach of blocking cancer migration followed by photodynamic killing using rationally designed nanomedicine is a promising new strategy against cancer metastasis.From the Clinical EditorA multifunctional core-shell nanomedicine capable of inhibiting metastatic cancer cell migration, in addition to inducing photodynamic effects, is described in this paper. The authors document cytotoxicity in approximately 99% of the studied metastatic breast cancer cells. Similar approaches would be a very welcome addition to the treatment protocols of advanced metastatic breast cancer and other types of neoplasms.