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Dang W, Xing B, Jia X, et al. Int J Nanomedicine. 2023;18:3047-3068. The authors have advised Figure 4 on page 3059 is incorrect. Due to an error at the time of figure assembly parts of Figure 4B and Figure 4C were inadvertently duplicated. The correct Figure 4 is shown below. Figure 4 (A) The wound healing of different formulations. (B) The pictures of migration and invasion. (C) Wound healing rate, migration rate and invasion rate. ***P < 0.001, *P < 0.05, results were expressed as mean ± SD, n = 3. The authors sincerely apologize for these errors and guarantee that this correction has no impact to the interpretation of the presented results and conclusions of this work.

Wenli Dang,1– 3 Bin Xing,1– 3 Xintao Jia,1– 3 Ying Zhang,1– 3 Bei Jia,1– 3 Changxiang Yu,1– 3 Jiachen He,1– 3 Ziwei Li,1– 3 Huihui Li,1– 3 Zhidong Liu1– 3 1State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 3Haihe Laboratory of Modern Chinese Medicine, Tianjin, People’s Republic of ChinaCorrespondence: Zhidong Liu, Tianjin University of Traditional Chinese Medicine, No. 10 Poyang Lake Road, 301617, Tuanbo New Town, Jinghai District, Tianjin, People’s Republic of China, Tel +86 22-59596170, Email lonerliuzd@163.comBackground: Subcellular organelle targeted nano-formulations for cancer treatment are receiving increasing attention owing to their benefits of precise drug delivery, maximized therapeutic index, and reduced off-target side effects. The nucleus and mitochondria, as the main subcellular organelles, are the significant organelles responsible for maintaining cell operation and metabolism. They can be involved in many essential physiological and pathological processes such as cell proliferation, organism metabolism, intracellular transportation, and play a critical role in regulating cell biology. Meanwhile, breast cancer metastasis is one of the leading causes of death in breast cancer patients. With the development of nanotechnology, nanomaterials have been widely used in tumor therapy.Methods: We designed a subcellular organelle targeted nanostructured lipid carriers (NLC) to deliver paclitaxel (PTX) and gambogic acid (GA) to tumor tissues.Results: Due to the surface of NLC being modified by subcellular organelle targeted peptide, the PTX and GA co-loaded NLC can accurately release PTX and GA in tumor cells. This property makes NLC abl

Zhidong Liu,1 Miao Wang,1 Chunbo Zhang,2 Shigao Zhou,1 Guang Ji3 1Department of Internal Medicine of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 2School of Pharmacy, Nanchang University, Nanchang, Jiangxi, 330031, People’s Republic of China; 3Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of ChinaCorrespondence: Guang Ji, Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Road, Shanghai, 200032, People’s Republic of China, Tel +86 18156416071, Fax +86 21-64385700, Email jiliver@vip.sina.comAbstract: Ceruloplasmin (CP) is a multicopper oxidase and antioxidant that is mainly produced in the liver. CP not only plays a crucial role in the metabolic balance of copper and iron through its oxidase function but also exhibits antioxidant activity. In addition, CP is an acute-phase protein. In addition to being associated with aceruloplasminemia and neurodegenerative diseases such as Wilson’s disease, Alzheimer’s disease, and Parkinson’s disease, CP also plays an important role in metabolic diseases, which are caused by metabolic disorders and vigorous metabolism, mainly including diabetes, obesity, hyperlipidemia, etc. Based on the physiological functions of CP, we provide an overview of the association of type 2 diabetes, obesity, hyperlipidemia, coronary heart disease, CP oxidative stress, inflammation, and metabolism of copper and iron. Studies have shown that metabolic diseases are closely related to systemic inflammation, oxidative stress, and disorders of copper and iron metabolism. Therefore, we conclude that CP, which can reduce the formation of free radicals in tissues, can be induced during inflammation and infection, and can correct the metabolic disorder of copper and iron, has protectiv

Immature neurons generated by the subpallial MGE tangentially migrate to the cortex where they become parvalbumin-expressing (PV+) and somatostatin (SST+) interneurons. Here, we show that the Sp9 transcription factor controls the development of MGE-derived cortical interneurons. SP9 is expressed in the MGE subventricular zone and in MGE-derived migrating interneurons. Sp9 null and conditional mutant mice have approximately 50% reduction of MGE-derived cortical interneurons, an ectopic aggregation of MGE-derived neurons in the embryonic ventral telencephalon, and an increased ratio of SST+/PV+ cortical interneurons. RNA-Seq and SP9 ChIP-Seq reveal that SP9 regulates MGE-derived cortical interneuron development through controlling the expression of key transcription factors Arx, Lhx6, Lhx8, Nkx2-1, and Zeb2 involved in interneuron development, as well as genes implicated in regulating interneuron migration Ackr3, Epha3, and St18. Thus, Sp9 has a central transcriptional role in MGE-derived cortical interneuron development.

We present the case of a 71-year-old man admitted because of chest tightness, palpitations, and progressive shortness of breath. The diagnosis of severe aortic stenosis, coarctation, and aneurysm was established, as well as severely depressed left ventricular ejection fraction. Three consecutive transcatheter procedures were successfully performed in a single session. (Level of Difficulty: Advanced.)

Zhe Ma,1,2 Yuqi Fan,2,3 Yumei Wu,1,2 Dereje Kebebe,1,2,4 Bing Zhang,1,2 Peng Lu,1,2 Jiaxin Pi,1,2 Zhidong Liu1,2 1Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; 2Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; 3School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; 4School of Pharmacy, Institute of Health Sciences, Jimma University, Jimma, Ethiopia Abstract: Cancer is a major public health problem, and is now the world’s leading cause of death. Traditional Chinese medicine (TCM)-combination therapy is a new treatment approach and a vital therapeutic strategy for cancer, as it exhibits promising antitumor potential. Nanotargeted drug-delivery systems have remarkable advantages and allow the development of TCM-combination therapies by systematically controlling drug release and delivering drugs to solid tumors. In this review, the anticancer activity of TCM compounds is introduced. The combined use of TCM for antitumor treatment is analyzed and summarized. These combination therapies, using a single nanocarrier system, namely codelivery, are analyzed, issues that require attention are determined, and future perspectives are identified. We carried out a systematic review of >280 studies published in PubMed since 1985 (no patents involved), in order to provide a few basic considerations in terms of the design principles and management of targeted nanotechnology-based TCM-combination therapies. Keywords: cancer, codelivery, combination therapy, nanotargeted drug-delivery system, tumor targeting, TCM

Hongli Yan,1,2,* Zhifeng Xue,1,2,* Jiarong Xie,1,2 Yixiao Dong,1,2 Zhe Ma,1,2 Xinru Sun,1,2 Dereje Kebebe Borga,1–3 Zhidong Liu,1,2 Jiawei Li2,4 1Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, People’s Republic of China; 2Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, People’s Republic of China; 3School of Pharmacy, Institute of Health Sciences, Jimma University, Jimma, Ethiopia; 4Institute of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhidong LiuTianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 10, Poyang Lake Road, Jinghai, Tianjin 301617, People’s Republic of ChinaTel +86 22 5959 6163Email lonerliuzd@163.comJiawei LiInstitute of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, No. 10, Poyang Lake Road, Jinghai, Tianjin 301617, People’s Republic of ChinaTel +86 22 5959 6352Email lijiawei1981@163.comAbstract: Nanoparticle drug formulations have enormous application prospects owing to achievement of targeted and sustained release drug delivery, improvement in drug solubility and reduction of adverse drug reactions. Recently, a variety of efficient drug nanometer carriers have been developed, among which carbon nanotubes (CNT) have been increasingly utilized in the field of cancer therapy. However, these nanotubes exert various toxic effects on the body due to their unique physical and chemical properties. CNT-induced toxicity is related to surface modification, degree of aggregation in vivo, and nanoparticle concentration. This review has focused on the potential toxic effects of CNTs ut

Dereje Kebebe,1–3,* Yumei Wu,1,2,* Bing Zhang,1,2 Jian Yang,1,2 Yuanyuan Liu,1,2 Xinyue Li,1,2 Zhe Ma,1,2 Peng Lu,1,2 Zhidong Liu,1,2 Jiawei Li1,21Tianjin State Key Laboratory of Modern Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, People’s Republic of China; 2Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, People’s Republic of China; 3Department of Pharmaceutics, School of Pharmacy, Institute of Health Sciences, Jimma University, Jimma, Ethiopia*These authors contributed equally to this workBackground and purpose: Gambogic acid (GA) is a natural compound that exhibited a promising multi-target antitumor activity against several types of cancer. However, the clinical application of this drug is limited due to its poor solubility and low tumor cell-specific delivery. In this study, the monomeric and dimeric Cyclo (Arg-Gly-Asp) c(RGD) tumor targeting peptides (c(RGDfK) and E-[c(RGDfK)2]) were used to modify GA loaded nanostructured lipid carriers (NLC) to reduce the limitations associated with GA and improve its antitumor activity.Methods: GA-NLC was prepared by emulsification and solvent evaporation methods and the surface of the NLC was conjugated with the c(RGD) peptides via an amide bond. The formulations were characterized for particle size, morphology and zeta potential, encapsulation efficiency and drug loading. The in-vitro cytotoxicity and cell uptake studies were conducted using 4T1 cell. Furthermore, the in-vivo antitumor activity and bio-distribution study were performed on female BALB/c nude mice.Results: The c(RGD) peptides modified GA-NLC was successfully prepared with the particles size about 20 nm. The HPLC analysis, FT-IR and 1H-NMR spectra confirmed the successful conjugation of the pepti

Hongli Yan,1,2,* Zhifeng Xue,1,2,* Jiarong Xie,1,2 Yixiao Dong,1,2 Zhe Ma,1,2 Xinru Sun,1,2 Dereje Kebebe Borga,1–3 Zhidong Liu,1,2 Jiawei Li2,4 1Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, People’s Republic of China; 2Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, People’s Republic of China; 3School of Pharmacy, Institute of Health Sciences, Jimma University, Jimma, Ethiopia; 4Institute of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhidong LiuTianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 10, Poyang Lake Road, Jinghai, Tianjin 301617, People’s Republic of ChinaTel +86 22 5959 6163Email lonerliuzd@163.comJiawei LiInstitute of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, No. 10, Poyang Lake Road, Jinghai, Tianjin 301617, People’s Republic of ChinaTel +86 22 5959 6352Email lijiawei1981@163.comAbstract: Nanoparticle drug formulations have enormous application prospects owing to achievement of targeted and sustained release drug delivery, improvement in drug solubility and reduction of adverse drug reactions. Recently, a variety of efficient drug nanometer carriers have been developed, among which carbon nanotubes (CNT) have been increasingly utilized in the field of cancer therapy. However, these nanotubes exert various toxic effects on the body due to their unique physical and chemical properties. CNT-induced toxicity is related to surface modification, degree of aggregation in vivo, and nanoparticle concentration. This review has focused on the potential toxic effects of CNTs ut

Zhe Ma,1,2 Yuqi Fan,2,3 Yumei Wu,1,2 Dereje Kebebe,1,2,4 Bing Zhang,1,2 Peng Lu,1,2 Jiaxin Pi,1,2 Zhidong Liu1,2 1Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; 2Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; 3School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; 4School of Pharmacy, Institute of Health Sciences, Jimma University, Jimma, Ethiopia Abstract: Cancer is a major public health problem, and is now the world’s leading cause of death. Traditional Chinese medicine (TCM)-combination therapy is a new treatment approach and a vital therapeutic strategy for cancer, as it exhibits promising antitumor potential. Nanotargeted drug-delivery systems have remarkable advantages and allow the development of TCM-combination therapies by systematically controlling drug release and delivering drugs to solid tumors. In this review, the anticancer activity of TCM compounds is introduced. The combined use of TCM for antitumor treatment is analyzed and summarized. These combination therapies, using a single nanocarrier system, namely codelivery, are analyzed, issues that require attention are determined, and future perspectives are identified. We carried out a systematic review of >280 studies published in PubMed since 1985 (no patents involved), in order to provide a few basic considerations in terms of the design principles and management of targeted nanotechnology-based TCM-combination therapies. Keywords: cancer, codelivery, combination therapy, nanotargeted drug-delivery system, tumor targeting, TCM

Dereje Kebebe,1–3,* Yumei Wu,1,2,* Bing Zhang,1,2 Jian Yang,1,2 Yuanyuan Liu,1,2 Xinyue Li,1,2 Zhe Ma,1,2 Peng Lu,1,2 Zhidong Liu,1,2 Jiawei Li1,21Tianjin State Key Laboratory of Modern Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, People’s Republic of China; 2Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, People’s Republic of China; 3Department of Pharmaceutics, School of Pharmacy, Institute of Health Sciences, Jimma University, Jimma, Ethiopia*These authors contributed equally to this workBackground and purpose: Gambogic acid (GA) is a natural compound that exhibited a promising multi-target antitumor activity against several types of cancer. However, the clinical application of this drug is limited due to its poor solubility and low tumor cell-specific delivery. In this study, the monomeric and dimeric Cyclo (Arg-Gly-Asp) c(RGD) tumor targeting peptides (c(RGDfK) and E-[c(RGDfK)2]) were used to modify GA loaded nanostructured lipid carriers (NLC) to reduce the limitations associated with GA and improve its antitumor activity.Methods: GA-NLC was prepared by emulsification and solvent evaporation methods and the surface of the NLC was conjugated with the c(RGD) peptides via an amide bond. The formulations were characterized for particle size, morphology and zeta potential, encapsulation efficiency and drug loading. The in-vitro cytotoxicity and cell uptake studies were conducted using 4T1 cell. Furthermore, the in-vivo antitumor activity and bio-distribution study were performed on female BALB/c nude mice.Results: The c(RGD) peptides modified GA-NLC was successfully prepared with the particles size about 20 nm. The HPLC analysis, FT-IR and 1H-NMR spectra confirmed the successful conjugation of the pepti

Dereje Kebebe,1–4 Yuanyuan Liu,1–3 Yumei Wu,1–3 Maikhone Vilakhamxay,1–3 Zhidong Liu,1–3 Jiawei Li1–3 1Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; 2Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; 3Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China; 4School of Pharmacy, Institute of Health Sciences, Jimma University, Jimma, Ethiopia Abstract: Cancer has become one of the leading causes of mortality globally. The major challenges of conventional cancer therapy are the failure of most chemotherapeutic agents to accumulate selectively in tumor cells and their severe systemic side effects. In the past three decades, a number of drug delivery approaches have been discovered to overwhelm the obstacles. Among these, nanocarriers have gained much attention for their excellent and efficient drug delivery systems to improve specific tissue/organ/cell targeting. In order to enhance targeting efficiency further and reduce limitations of nanocarriers, nanoparticle surfaces are functionalized with different ligands. Several kinds of ligand-modified nanomedicines have been reported. Cell-penetrating peptides (CPPs) are promising ligands, attracting the attention of researchers due to their efficiency to transport bioactive molecules intracellularly. However, their lack of specificity and in vivo degradation led to the development of newer types of CPP. Currently, activable CPP and tumor-targeting peptide (TTP)-modified nanocarriers have shown dramatically superior cellular specific uptake, cytotoxicity, and tumor growth inhibition. In this review, we discuss recent advances in tumor-targeting strategies using CPPs and their limitations in tumor delivery

Dereje Kebebe,1–4 Yuanyuan Liu,1–3 Yumei Wu,1–3 Maikhone Vilakhamxay,1–3 Zhidong Liu,1–3 Jiawei Li1–3 1Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; 2Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; 3Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China; 4School of Pharmacy, Institute of Health Sciences, Jimma University, Jimma, Ethiopia Abstract: Cancer has become one of the leading causes of mortality globally. The major challenges of conventional cancer therapy are the failure of most chemotherapeutic agents to accumulate selectively in tumor cells and their severe systemic side effects. In the past three decades, a number of drug delivery approaches have been discovered to overwhelm the obstacles. Among these, nanocarriers have gained much attention for their excellent and efficient drug delivery systems to improve specific tissue/organ/cell targeting. In order to enhance targeting efficiency further and reduce limitations of nanocarriers, nanoparticle surfaces are functionalized with different ligands. Several kinds of ligand-modified nanomedicines have been reported. Cell-penetrating peptides (CPPs) are promising ligands, attracting the attention of researchers due to their efficiency to transport bioactive molecules intracellularly. However, their lack of specificity and in vivo degradation led to the development of newer types of CPP. Currently, activable CPP and tumor-targeting peptide (TTP)-modified nanocarriers have shown dramatically superior cellular specific uptake, cytotoxicity, and tumor growth inhibition. In this review, we discuss recent advances in tumor-targeting strategies using CPPs and their limitations in tumor delivery

Nan Li,1–3,* Zhenzhen Han,1,2,4,* Lin Li,1,2 Bing Zhang,1–3 Zhidong Liu,1–3 Jiawei Li1,2 1Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2Institute of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 3Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 4Baokang Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China *These authors contributed equally to this work Purpose: The objective of this study was to investigate the effects of the solid lipid nanoparticles of baicalin (BA-SLNs) on an experimental cataract model and explore the molecular mechanism combined with bioinformatics analysis.Materials and methods: The transparency of lens was observed daily by slit-lamp and photography. Lenticular opacity was graded. Two-dimensional gel electrophoresis (2-DE) was employed to analyze the differential protein expression modes in each group. Proteins of interest were subjected to protein identification by nano-liquid chromatography tandem mass spectrometry (LC–MS/MS). Bioinformatics analysis was performed using the Ingenuity Pathway Analysis (IPA) online software to comprehend the biological implications of the proteins identified by proteomics.Results: At the end of the sodium selenite-induced cataract progression, almost all lenses from the model group developed partial nuclear opacity; however, all lenses were clear and normal in the blank group. There was no significant difference between the BA-SLNs group and the blank group. Many protein spots were differently expressed in 2-DE patterns of total proteins of lenses from each group

Lingling Ding,1–3 Jiawei Li,1,2 Rui Huang,1,2 Zhidong Liu,1,2 Chunhua Li,1–3 Shaozi Yao,1,2 Jinyan Wang,1,2 Dongli Qi,1,2 Nan Li,1,2 Jiaxin Pi1,21Tianjin State Key Laboratory of Modern Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 2Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Tianjin University of Traditional Chinese Medicine, 3Tianjin International Joint Academy of Biomedicine, Tianjin, People’s Republic of ChinaAbstract: Targeted delivery by the folate ligand is an effective way to enhance an anti-breast carcinoma effect, due to its high affinity for the folate receptor, which is overexpressed in many tumor cells. In this study, we firstly synthesized a folic acid (FA)-targeted and polyethylene glycol (PEG)-modified TiO2 nanocarrier. Then, an FA-PEG-TiO2 nanoparticle (NP) codelivery system loaded with curcumin and salvianolic acid B were prepared by emulsion evaporation–solidification at low temperature. The obtained folate-targeted NPs (FA-NPs) showed more cytotoxicity on MCF7 cells and MDA-MB-231 cells than a nontargeted NP group. Apart from a synergistic anti-breast cancer effect with curcumin, salvianolic acid B protects the cardiovascular system from oxidative injury by the TiO2 nanocarrier. With coumarin 6 as a fluorescent probe to observe cellular uptake of NPs, the results of in vitro cellular uptake demonstrated FA-NPs exhibited higher cellular uptake and accumulation in MCF7 cells and MDA-MB-231 cells than nontargeted NPs. Then, in vivo biodistribution of NPs was further qualitatively and quantitatively confirmed by in vivo imaging. More importantly, the animal study further suggested that FA-NPs had significantly stronger antitumor effects via receptor-mediated targeted delivery. Consequently, FA-PEG-TiO2 NPs loaded with curcumin and salvianolic acid B could be a promising drug-delivery system to treat

Striatal medium-sized spiny neurons (MSNs), composed of striatonigral and striatopallidal neurons, are derived from the lateral ganglionic eminence (LGE). We find that the transcription factor Sp9 is expressed in LGE progenitors that generate nearly all striatal MSNs and that Sp9 expression is maintained in postmitotic striatopallidal MSNs. Sp9-null mice lose most striatopallidal MSNs because of decreased proliferation of striatopallidal MSN progenitors and increased Bax-dependent apoptosis, whereas the development of striatonigral neurons is largely unaffected. ChIP qPCR provides evidence that Ascl1 directly binds the Sp9 promoter. RNA-seq and in situ hybridization reveal that Sp9 promotes expression of Adora2a, P2ry1, Gpr6, and Grik3 in the LGE and striatum. Thus, Sp9 is crucial for the generation, differentiation, and survival of striatopallidal MSNs.

Lingling Ding,1–3 Jiawei Li,1,2 Rui Huang,1,2 Zhidong Liu,1,2 Chunhua Li,1–3 Shaozi Yao,1,2 Jinyan Wang,1,2 Dongli Qi,1,2 Nan Li,1,2 Jiaxin Pi1,21Tianjin State Key Laboratory of Modern Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 2Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Tianjin University of Traditional Chinese Medicine, 3Tianjin International Joint Academy of Biomedicine, Tianjin, People’s Republic of ChinaAbstract: Targeted delivery by the folate ligand is an effective way to enhance an anti-breast carcinoma effect, due to its high affinity for the folate receptor, which is overexpressed in many tumor cells. In this study, we firstly synthesized a folic acid (FA)-targeted and polyethylene glycol (PEG)-modified TiO2 nanocarrier. Then, an FA-PEG-TiO2 nanoparticle (NP) codelivery system loaded with curcumin and salvianolic acid B were prepared by emulsion evaporation–solidification at low temperature. The obtained folate-targeted NPs (FA-NPs) showed more cytotoxicity on MCF7 cells and MDA-MB-231 cells than a nontargeted NP group. Apart from a synergistic anti-breast cancer effect with curcumin, salvianolic acid B protects the cardiovascular system from oxidative injury by the TiO2 nanocarrier. With coumarin 6 as a fluorescent probe to observe cellular uptake of NPs, the results of in vitro cellular uptake demonstrated FA-NPs exhibited higher cellular uptake and accumulation in MCF7 cells and MDA-MB-231 cells than nontargeted NPs. Then, in vivo biodistribution of NPs was further qualitatively and quantitatively confirmed by in vivo imaging. More importantly, the animal study further suggested that FA-NPs had significantly stronger antitumor effects via receptor-mediated targeted delivery. Consequently, FA-PEG-TiO2 NPs loaded with curcumin and salvianolic acid B could be a promising drug-delivery system to treat