Hepatic solute carrier transporters and drug therapy: Regulation of expression and impact of genetic variation

Nies, Anne T.; Schaeffeler, Elke; Schwab, Matthias

doi:10.1016/j.pharmthera.2022.108268

Cited by 12 publications

(2 citation statements)

References 421 publications

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“…Although the targeting mechanism of such action remains to be elucidated, it may be related to organic anion transporter peptides (OATPs), which is known to mediate the transmembrane uptake of small molecule drugs and include structurally related fluorophores. [51][52][53] The intracellular uptake efficacy of DNPs and IDNPs was compared by the fluorescence shift of DOX. From Figure 2b, we found that the fluorescence in the IDNPs group is significantly enhanced compared with the DNPs group at the same time of incubation.…”

Section: Intracellular Uptake Of Idnps and In Vitro Chemo-phototherma...mentioning

confidence: 99%

Multifunctional Nanoplatform-Mediated Chemo-Photothermal Therapy Combines Immunogenic Cell Death with Checkpoint Blockade to Combat Triple-Negative Breast Cancer and Distant Metastasis

Zhu¹,

Ke²,

Yao³

et al. 2023

IJN

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Background Breast cancer has become the most common cancer in women. Compare with other subtypes of breast cancer, triple-negative breast cancer (TNBC) is more likely to relapse and metastasize. Highly effective therapeutic strategies are desperately needed to be explored. In this study, a multifunctional nanoplatform is expected to mediate chemo-photothermal therapy, which can combine immunogenic cell death with checkpoint blockade to combat TNBC and distant metastasis. Methods Poly (lactic acid-glycolic acid)-Poly (ethylene glycol) (PLGA-PEG) nanoparticles (NPs), a type of polymeric NPs, loaded with IR780, a near-infrared (NIR) dye, and doxorubicin (DOX) as the chemotherapeutic drug, were assembled by an improved double emulsification method (designated as IDNPs). The characterization, intracellular uptake, biosafety, photoacoustic (PA) imaging performance, and biodistribution of IDNPs were studied. Chemo-photothermal therapeutic effect and immunogenic cell death (ICD) were evaluated both in vitro and in vivo. The potency of chemo-photothermal therapy-triggered ICD in combination with anti-PD-1 immune checkpoint blockade (ICB) immunotherapy in eliciting immune response and treating distant tumors was further investigated. Results IR780 and DOX were successfully loaded into PLGA-PEG to form the IDNPs, with size of 243.87nm and Zeta potential of −6.25mV. The encapsulation efficiency of IR780 and DOX was 83.44% and 5.98%, respectively. IDNPs demonstrated remarkable on-site accumulation and PA imaging capability toward 4T1 TNBC models. Chemo-photothermal therapy demonstrated satisfactory therapeutic effects both in vitro and in vivo, and triggered ICD efficiently. ICD, in combination with anti-PD-1, provoked a systemic antitumor immune response against distant tumors. Conclusion Multifunctional IDNPs were successfully synthesized to mediate chemo-photothermal therapy, which combines immunogenic cell death with checkpoint blockade to combat TNBC and distant metastasis, showing great promise preclinically and clinically.

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Section: Intracellular Uptake Of Idnps and In Vitro Chemo-phototherma...mentioning

confidence: 99%

Multifunctional Nanoplatform-Mediated Chemo-Photothermal Therapy Combines Immunogenic Cell Death with Checkpoint Blockade to Combat Triple-Negative Breast Cancer and Distant Metastasis

Zhu¹,

Ke²,

Yao³

et al. 2023

IJN

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“…Then, Slco1a4, a membrane transporter, stood out. Slco1a4, also known as Oatp1a4, is a member of the solute carrier organic anion transporter family [12]. Several studies have revealed that Slco1a4 is involved in the hepatic uptake of a wide range of substrate drugs [13,14].…”

Section: Introductionmentioning

confidence: 99%

Generation of Slco1a4-CreERT2-tdTomato Knock-in Mice for Specific Cerebrovascular Endothelial Cell Targeting

Xu,

Li,

Cai

et al. 2024

IJMS

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The cerebrovascular endothelial cells with distinct characteristics line cerebrovascular blood vessels and are the fundamental structure of the blood–brain barrier, which is important for the development and homeostatic maintenance of the central nervous system. Cre-LoxP system-based spatial gene manipulation in mice is critical for investigating the physiological functions of key factors or signaling pathways in cerebrovascular endothelial cells. However, there is a lack of Cre recombinase mouse lines that specifically target cerebrovascular endothelial cells. Here, using a publicly available single-cell RNAseq database, we screened the solute carrier organic anion transporter family member 1a4 (Slco1a4) as a candidate marker of cerebrovascular endothelial cells. Then, we generated an inducible Cre mouse line in which a CreERT2-T2A-tdTomato cassette was placed after the initiation codon ATG of the Slco1a4 locus. We found that tdTomato, which can indicate the endogenous Slco1a4 expression, was expressed in almost all cerebrovascular endothelial cells but not in any other non-endothelial cell types in the brain, including neurons, astrocytes, oligodendrocytes, pericytes, smooth muscle cells, and microglial cells, as well as in other organs. Consistently, when crossing the ROSA26LSL-EYFP Cre reporter mouse, EYFP also specifically labeled almost all cerebrovascular endothelial cells upon tamoxifen induction. Overall, we generated a new inducible Cre line that specifically targets cerebrovascular endothelial cells.

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Impact of liver diseases and pharmacological interactions on the transportome involved in hepatic drug disposition

Marin,

Cives-Losada,

Macias

et al. 2024

Biochemical Pharmacology

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Hepatic solute carrier transporters and drug therapy: Regulation of expression and impact of genetic variation

Cited by 12 publications

References 421 publications

Multifunctional Nanoplatform-Mediated Chemo-Photothermal Therapy Combines Immunogenic Cell Death with Checkpoint Blockade to Combat Triple-Negative Breast Cancer and Distant Metastasis

Multifunctional Nanoplatform-Mediated Chemo-Photothermal Therapy Combines Immunogenic Cell Death with Checkpoint Blockade to Combat Triple-Negative Breast Cancer and Distant Metastasis

Generation of Slco1a4-CreERT2-tdTomato Knock-in Mice for Specific Cerebrovascular Endothelial Cell Targeting

Impact of liver diseases and pharmacological interactions on the transportome involved in hepatic drug disposition

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