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. 2020 Mar 5;96(2):260–279. doi: 10.1111/php.13217

Table 1.

List of theranostic nanomaterials that deliver photosensitizer and also act as US and/or photoacoustic contrast agents

Nanomaterial Model Photosensitizer dose/DLI Imaging parameters Tumor targeting Ref
Nanoagents for US contrast and delivering PS
Porphyrin‐grafted lipid microbubble (PGL‐MB)

PC3 Human prostate cancer xenograft in mice

Porphyrin 650 nm, 200  mW.cm−2 4  h after low‐ frequency US (LFUS)

US @ 1 MHz to monitor NP accumulation at tumor Porphyrin‐tumor affinity, US‐targeted microbubble destruction (UTMD) 88
Ce6‐loaded CaCO3 core and PEG shell

MCF‐7 Human breast cancer in vitro

Ce6

671 nm, 6 J.cm−2

0 h DLI

US @ 40 MHz to assess NP’s US contrast for 3 h CaCO3 causing PS release at tumoral pH 89
Porphyrin‐grafted lipid (CPGL) microbubble loaded with HIF 1α siRNA (siHIF@CpMB) MDA‐MB‐231 Human breast cancer injected in mice

Porphyrin

650 nm, 200 mW.cm−2

6 h DLI

US @ 3‐12 MHz to monitor MB uptake in tumor Porphyrin‐tumor affinity, UTMD 90
Nanoagents for photoacoustic contrast and delivering PS
Dox‐loaded, folate receptors α (FRα) targeted MTX‐decorated self‐assembled zinc phthalocyanine–soybean phospholipid complex NPs (DZSM)

4T1

Human breast cancer cells

Subcutaneous tumors

ZnPc‐SPC (ZS) complex

638 nm, 1000 mW.cm−2

24 h DLI

PA imaging @ 638 nm to monitor DZSM accumulation at tumor site Folic acid (FA) receptor‐mediated tumor uptake 140
Hyaluronic acid (HA) coupled with chlorin e6 (Ce6) via adipic dihydrazide (ADH) forming HA‐ADH‐Ce6 conjugates and self‐assembly into HACE NPs.

A549

Human lung cancer Subcutaneous tumors

Ce6 660 nm, 160 mW.cm−2 24 h DLI

PA imaging @ 680 nm to monitor HACE NP accumulation at tumor HA specificity to CD44 on tumor 127
Ce6 bound to HA nanoparticle with perfluorohexane core (PFH@HSC) MDA‐MB‐231 Human breast cancer Subcutaneous tumors

Ce6

660 nm, 100 mW.cm−2

4 h DLI

PA imaging @ 690‐900 nm to monitor hypoxia relief and PFH@HSC accumulation at tumor EPR and HA specificity to CD44 on tumor 128
Diketopyrrolopyrrole (DPP)–triphenylamine (TPA) NP HTC‐116 Human colorectal cancer cells Subcutaneous tumors

DPP‐TPA

660 nm, 1 W.cm−2

2 h DLI

PA imaging @ 680 nm to monitor DPP‐TPA NP accumulation at tumor EPR and PA‐guided activation 129
Perylene diimide zwitterionic polymer (PDS‐PDI) MDA‐MB‐231 Human breast cancer injected in mice

Perylene‐3,4,9,10‐tetracarboxylic diimide (PDS)

660 nm, 500 mW.cm−2

6 h DLI

PA imaging @ 660 nm to monitor PDS‐PDI accumulation at tumor EPR and PA‐guided activation 103
Tellurium nanosheets functionalized with glutathione (GSH) HepG2 Human liver cancer injected into mice

Te nanosheets

670 nm, 160 mW.cm−2

0 h DLI

PA imaging @ 680‐980 nm to confirm tumor uptake of Te nanosheets + GSH EPR and PA‐guided activation 100
Cell membrane‐derived shell and a methylene blue and cisplatin (Pt) loaded gelatin nanogel core (MPV) 4T1 Murine breast cancer orthotopic tumors in mice

Methylene blue

671 nm, 450 mW.cm−2

1 h and 4 h DLI

PA imaging @ 680 nm to monitor intratumoral deposition of MPV EPR and PA‐guided activation 130
Pc core and four ethanolamine and phthalocyanine‐difunctionalized poly(glycidyl methacrylate) arms NP (Pc‐PGEA/Pc‐3) containing p53 C6 Rat glioma injected in mice

Pc‐PGEA/Pc NPs

700 nm, 800 mW.cm−2

0 h DLI

PA imaging @ 680‐980 nm to monitor Pc‐PGEA/Pc accumulation at tumor EPR and PA‐guided activation 131
BODIPY within amphiphilic DSPE‐mPEG5000 A549 Human lung cancer subcutaneously injected in mice

BODIPY

730 nm, 200 mW.cm−2

0.5 h DLI

PA imaging @ 760 nm to assess enhanced permeability and retention (EPR) and lysosomal accumulation of BODIPY NP Direct injection, BODIPY accumulation in acidic lysosomes 132
Lecithin/DSPE‐PEG‐FA outer shell containing PCM core housing DOX and diketopyrrolopyrrole (DPP)‐BT dye, functionalized with FA (P(DPPBT/DOX) NP) HeLa Human cervical cancer subcutaneously injected into mice

DPP‐BT

730 nm, 1000 mW.cm−2

24 h DLI

PA imaging @ 730 nm to monitor P(DPP‐BT/DOX) NP accumulation at tumor FA receptor‐mediated tumor uptake 133
Silicon 2,3‐naphthalocyanine bi(trihexylsilyloxide) (SiNc) HT‐29 Human colorectal cancer injected into mice

SiNC

770nm, 40 mJ

.08 – 1 h DLI

PA imaging @ 680‐860 nm to monitor SiNC presence in tumor and assessment of SiNC PA signal strength EPR 134
Porphyrin‐ or phthalocyanine‐bridged silsesquioxane nanoparticles (BSPOR and BSPHT) MCF‐7 Human breast cancer cells in vitro

BSPOR/BSPHT

800 nm, 4300 mW.cm−2

24 h DLI

PA imaging @ 700 nm to monitor BSPOR and BSPHT accumulation at tumor Porphyrin‐tumor affinity 135
Artificial red blood cell loaded with oxygen (IARC) MCF‐7 Human breast cancer injected into mice

ICG

808 nm, 100 mW.cm−2

0.5 h DLI

Spectroscopic PA imaging to monitor ICG, HbO2 and Hb accumulation at tumor EPR 109
ICG‐loaded PEGylated silver nanoparticle core/polyaniline shell (Ag@PANI) nanocomposites (ICG‐Ag@PANI) HeLa Human cervical cancer subcutaneously injected into mice

ICG 808 nm/1000 mW.cm−2

24 h DLI

PA imaging @ 808 nm to monitor accumulation of ICG‐Ag@PANI at tumor EPR 136

ICG‐HA nanoparticle embedded with single‐walled carbon nanotubes ICGHANP/SWCNTs (IHANPT)

SSC7 Human oral cancer subcutaneously injected in mice

ICG

808 nm/800 mW.cm‐2

24 h DLI

PA imaging @ 808 nm to monitor IHANP accumulation at tumor EPR and IHANPT specificity to CD44 on tumor 137
MgO2 NP in ICG and hyaluronic acid (HA) NP SSC7 Human oral cancer xenografted in mice

ICG

808 nm, 800 mW.cm−2

6 h DLI

PA imaging @ 808 nm to monitor NP accumulation at tumor HA specificity to CD44 on tumor 107
Hyaluronic acid (HA)–cystamine–cholesterol (HSC) self‐assembling conjugate incorporating IR780 (HSCI NPs) MDA‐MB‐231 Human breast cancer injected in mice

IR780

808 nm, 800 mW.cm−2

0 h DLI

PA imaging @ 680‐980 nm to monitor HSCI NP accumulation at tumor EPR and HA specificity to CD44 on tumor 138
Iridium‐cyanine nanoparticle (IrCy) 4T1 Murine breast cancer syngeneic xenografts in mice

Iridium dye

808 nm, 50 mW.cm−2

24 h DLI followed by IrCy readministration at 48 h and PDT at 72 h

PA imaging @ 815 nm for detecting cyanine dye to monitor biodistribution and accumulation of IrCy at tumor EPR and PA‐guided activation 139

Cu‐Sb‐S functionalized with poly(vinylpyrrolidone)

(PVP‐Cu‐Sb‐S) NP

4T1 Murine breast cancer syngeneic xenografts in mice

PVP‐Cu‐Sb‐S NP

808 nm, 1000 mW.cm−2

0 h DLI

PA imaging @ 808 nm for monitoring tumor uptake of PVP‐Cu‐Sb‐S NPs EPR and PA‐guided activation 102
Zinc(II)‐phthalocyanine nanodots, PEG‐folate/ZnPc nanodots (FA‐ZnPcNDs) CNE‐2 Human nasopharyngeal cancer injected into mice

ZnPC

808 nm, 500 mW.cm−2

2 h DLI

PA imaging @ 808 nm to monitor FA‐ZnPcND accumulation at tumor FA receptor‐mediated tumor uptake 101
Polypyrrole with astaxanthin‐conjugated bovine serum albumin polymer (PPy@BSA‐Astx)

MBA‐MD‐231 Human breast cancer

in vitro

Astaxanthin

808 nm, 300 mW.cm−2

6 h DLI

PA @ 808 nm to monitor PPy@BSA‐Astx US signal production Passive targeting 141