title: Reporter nanoparticle that monitors its anticancer efficacy in real time.
abstract: The ability to monitor the efficacy of an anticancer treatment in real time can have a critical effect on the outcome. Currently, clinical readouts of efficacy rely on indirect or anatomic measurements, which occur over prolonged time scales postchemotherapy or postimmunotherapy and may not be concordant with the actual effect. Here we describe the biology-inspired engineering of a simple 2-in-1 reporter nanoparticle that not only delivers a cytotoxic or an immunotherapy payload to the tumor but also reports back on the efficacy in real time. The reporter nanoparticles are engineered from a novel two-staged stimuli-responsive polymeric material with an optimal ratio of an enzyme-cleavable drug or immunotherapy (effector elements) and a drug function-activatable reporter element. The spatiotemporally constrained delivery of the effector and the reporter elements in a single nanoparticle produces maximum signal enhancement due to the availability of the reporter element in the same cell as the drug, thereby effectively capturing the temporal apoptosis process. Using chemotherapy-sensitive and chemotherapy-resistant tumors in vivo, we show that the reporter nanoparticles can provide a real-time noninvasive readout of tumor response to chemotherapy. The reporter nanoparticle can also monitor the efficacy of immune checkpoint inhibition in melanoma. The self-reporting capability, for the first time to our knowledge, captures an anticancer nanoparticle in action in vivo.
authors.affiliation: Laboratory of Nanomedicine, Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115; Division of Biomedical Engineering, Harvard Medical School, Boston, MA 02115; ashishk@mit.edu ram@ncl.res.in shiladit@mit.edu.
authors.forename: Ashish
authors.initials: A
authors.lastname: Kulkarni
authors.affiliation: Laboratory of Nanomedicine, Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115; Division of Biomedical Engineering, Harvard Medical School, Boston, MA 02115;
authors.forename: Poornima
authors.initials: P
authors.lastname: Rao
authors.affiliation: Laboratory of Nanomedicine, Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115; Division of Biomedical Engineering, Harvard Medical School, Boston, MA 02115;
authors.forename: Siva
authors.initials: S
authors.lastname: Natarajan
authors.affiliation: Laboratory of Nanomedicine, Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115; Division of Biomedical Engineering, Harvard Medical School, Boston, MA 02115;
authors.forename: Aaron
authors.initials: A
authors.lastname: Goldman
authors.affiliation: Division of Renal (Kidney) Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Venkata S
authors.initials: VS
authors.lastname: Sabbisetti
authors.affiliation: Laboratory of Nanomedicine, Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115; Division of Biomedical Engineering, Harvard Medical School, Boston, MA 02115;
authors.forename: Yashika
authors.initials: Y
authors.lastname: Khater
authors.affiliation: Laboratory of Nanomedicine, Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115; Division of Biomedical Engineering, Harvard Medical School, Boston, MA 02115;
authors.forename: Navya
authors.initials: N
authors.lastname: Korimerla
authors.affiliation: Laboratory of Nanomedicine, Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115; Division of Biomedical Engineering, Harvard Medical School, Boston, MA 02115;
authors.forename: Vineethkrishna
authors.initials: V
authors.lastname: Chandrasekar
authors.affiliation: National Chemical Laboratory, Pune 411008, India; ashishk@mit.edu ram@ncl.res.in shiladit@mit.edu.
authors.forename: Raghunath A
authors.initials: RA
authors.lastname: Mashelkar
authors.affiliation: Laboratory of Nanomedicine, Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115; Division of Biomedical Engineering, Harvard Medical School, Boston, MA 02115; Dana Farber Cancer Institute, Boston, MA 02115 ashishk@mit.edu ram@ncl.res.in shiladit@mit.edu.
authors.forename: Shiladitya
authors.initials: S
authors.lastname: Sengupta
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D060890:B7-H1 Antigen / Q000276:immunology; D053148:Caspase 3 / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D016903:Drug Monitoring / Q000379:methods*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004950:Esterases / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D015166:Monitoring, Immunologic / Q000379:methods*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D004337:Drug Carriers; D005456:Fluorescent Dyes; D007074:Immunoglobulin G; D009842:Oligopeptides; D011108:Polymers; C512882:poly(isobutylene-alt-maleic acid); D004950:Esterases; D053148:Caspase 3; D017239:Paclitaxel
keywords: chemotherapy; immunotherapy; monitoring; nanoparticle; reporter