2019
DOI: 10.1021/acs.molpharmaceut.8b01157
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Doxorubicin and Anti-PD-L1 Antibody Conjugated Gold Nanoparticles for Colorectal Cancer Photochemotherapy

Abstract: Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. The prognosis and overall survival of CRC are known to be significantly correlated with the overexpression of PD-L1. Since combination therapies can significantly improve therapeutic efficacy, we constructed doxorubicin (DOX) conjugated and anti-PD-L1 targeting gold nanoparticles (PD-L1-AuNP-DOX) for the targeted chemo-photothermal therapy of CRC. DOX and anti-PD-L1 antibody were conjugated to the α-terminal end group of lipo… Show more

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Cited by 140 publications
(78 citation statements)
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“…Immunotoxin‐based anti‐PD‐L1 mAb is considered to be an effective tumor treatment method in theory, because: (i) the immune checkpoint protein PD‐L1 is broadly expressed in many cancers, 9,20,26,27 which is spectral in treatment; (ii) its expression is limited in tumor area but not in normal cells, the treatment is mainly aimed at tumor tissue, which makes PD‐L1‐specific treatment more accurate, and its side‐effects limited; (iii) ELISA assay showed that PD‐L1, as a transmembrane protein, was not released from the constitutively expressing PD‐L1 cell membrane; and (iv) the key is that PD‐L1 on tumor cells is glycosylated, so when anti‐PD‐L1 mAb is combined in the glycosylated domain, it will produce internalization, 28 which provides a good antitumor basis for IT‐based treatment 28,29 . At present, PD‐L1‐specific treatment, such as PDL1‐Dox 30 and PD‐L1‐AuNP‐DOX 31 in the form of an Ab‐drug conjugate, have shown some promising results. However, few studies focus on the generation of PD‐L1 by ITs.…”
Section: Discussionmentioning
confidence: 99%
“…Immunotoxin‐based anti‐PD‐L1 mAb is considered to be an effective tumor treatment method in theory, because: (i) the immune checkpoint protein PD‐L1 is broadly expressed in many cancers, 9,20,26,27 which is spectral in treatment; (ii) its expression is limited in tumor area but not in normal cells, the treatment is mainly aimed at tumor tissue, which makes PD‐L1‐specific treatment more accurate, and its side‐effects limited; (iii) ELISA assay showed that PD‐L1, as a transmembrane protein, was not released from the constitutively expressing PD‐L1 cell membrane; and (iv) the key is that PD‐L1 on tumor cells is glycosylated, so when anti‐PD‐L1 mAb is combined in the glycosylated domain, it will produce internalization, 28 which provides a good antitumor basis for IT‐based treatment 28,29 . At present, PD‐L1‐specific treatment, such as PDL1‐Dox 30 and PD‐L1‐AuNP‐DOX 31 in the form of an Ab‐drug conjugate, have shown some promising results. However, few studies focus on the generation of PD‐L1 by ITs.…”
Section: Discussionmentioning
confidence: 99%
“…aunPs coated with an anti-Her2 monoclonal antibody (trastuzumab)-cytotoxic drug [monomethyl auristatin e (MMae)] conjugate and a cell-penetrating peptide (HiV Tat) have been indicated to target Her-2-positive cells, increase cellular uptake and enhance the antimitotic potency and therapeutic index of free MMae in vitro (60). anti-eGFr-coated 5-fluorouracil-aunPs have also been revealed to target colorectal cancer cells that overexpress eGFr, increase their apoptosis rate and improve their anti-tumor effects (9). doX and anti-Pd-l1 antibody-conjugated aunPs enable drug delivery and PTT to target and induce cT-26 cellular apoptosis and inhibit cell proliferation (9).…”
Section: Development Of Aunps For Antineoplastic Drug Deliverymentioning
confidence: 99%
“…examples include abraxane, which was synthesized by attaching six or seven paclitaxel molecules to albumin nPs of 130-nm diameter, and is considered to be among the most successful nanotherapeutics, as it has been approved as a first-line treatment for non-small cell lung carcinoma by the uS Food and drug administration (8). Folic acid (Fa)-poly nPs have been prepared to target ovarian tumor tissue, and nPs that carry rituximab and paclitaxel have been designed to target cd20-positive B-cell lymphoma (9).…”
Section: Introductionmentioning
confidence: 99%
“…To maintain the temperature of the human body at 36−37 °C, the heat generated and lost should be balanced. (1) Therefore, thermoregulation plays a key role in maintaining the body temperature.…”
Section: Body Temperaturementioning
confidence: 99%