Mn-porphyrin Conjugated Au Nanoshells Encapsulating Doxorubicin for Potential Magnetic Resonance Imaging and Light Triggered Synergistic Therapy of Cancer

Abstract

A theranostic agent was successfully fabricated by the formation of Au nanoshell around poly(lactic acid) nanoparticles entrapping doxorubicin, followed by linking a Mn-porphyrin derivative on the Au shell surface through polyethylene glycol. The resulted agent exhibited excellent colloidal stability and long blood circulation time due to introducing polyethylene glycol. The grafting Mn-porphyrin onto the nanoparticle surface endowed a greatly improved relaxivity (r1 value of 22.18 mM-1s-1 of Mn3+), favorable for accurate cancer diagnosing and locating the tumor site to guide the external near infrared (NIR) laser irradiation for photothermal ablation of tumors. The in vitro experiments confirmed that the agent exhibited an efficient photohyperthermia and a light triggered and stepwise release behavior of doxorubicin due to the high NIR light absorption coefficient of Au nanoshell. The in vivo experiments showed that the combination of chemotherapy and photothermal therapy through such theranostic agent offered a synergistically improved therapeutic outcome compared with either therapy alone, making it a promising approach for cancer therapy. Therefore, such theranostic agent can be developed as a smart and promising nanosystemplatform that integrates multiple capabilities for both effective contrast enhanced magnetic resonance imaging and synergistic therapy.

Theranostic nanosensitizers for highly efficient MR/fluorescence imaging‐guided sonodynamic therapy of gliomas

“…27,[34][35][36][37] In our study, the r 1 value for DVDMS-Mn-LPs was about 4-fold higher than that of the clinical approved Magnevist due to increased local concentration of Mn 2+ and lowered molecular tumbling rate in those nanocarrier systems. [34][35][36][37] Given that the generation of ROS plays an important role in SDT of tumour treatment, the potential of DVDMS-Mn-LPs to generate ROS was determined using 2′, 7′-dichlorofluorescin diacetate as a typical probe. 23,8 The probe will be deacetylated by cellular esterases to non-fluorescent 2′,7′-Dichlorodihydrofluorescin (DCFH), which is rapidly oxidized to highly fluorescent 2′,7′-Dichlorodihydrofluorescein (DCF) by ROS.…”

“…The optical and T 1 relaxation properties of DVDMS‐Mn‐LPs hold promises for dual‐mode contrast agent for fluorescence and MR imaging of tumours (Figure ). In fact, abundant macromolecules and nanoparticles have been used as platforms for manganese loading, resulting in improved r 1 value of chelated Mn 2+ (generally between 5 and 30 per mmol/L per seconds) . In our study, the r 1 value for DVDMS‐Mn‐LPs was about 4‐fold higher than that of the clinical approved Magnevist due to increased local concentration of Mn 2+ and lowered molecular tumbling rate in those nanocarrier systems .…”

“…In fact, abundant macromolecules and nanoparticles have been used as platforms for manganese loading, resulting in improved r 1 value of chelated Mn 2+ (generally between 5 and 30 per mmol/L per seconds) . In our study, the r 1 value for DVDMS‐Mn‐LPs was about 4‐fold higher than that of the clinical approved Magnevist due to increased local concentration of Mn 2+ and lowered molecular tumbling rate in those nanocarrier systems . Given that the generation of ROS plays an important role in SDT of tumour treatment, the potential of DVDMS‐Mn‐LPs to generate ROS was determined using 2′, 7′‐dichlorofluorescin diacetate as a typical probe .…”

Emerging applications of porphyrins in photomedicine

“…[11]; (E) PpIX-modified mesoporous silica nanoparticle [12]; (F) Pd-porphyrin cross-linked hydrogel [13]; (G) In vivo MRI image of Mn-porphyrin nanoparticles [14]; (H) microPET/CT image of orthotopic PC3 tumor model after injection with 64 Cu-porphysomes [15]; (I) Fluorescence tracking of macrophages after injection of porphyrin-modified nanoparticles [16]; (J) Human esophageal cancer treated with PDT [17]; (K) Thermal images of tumor-bearing mice with Pc-loaded nanoparticles exposed to a NIR laser [18]; (L) 8 h (a1) and 24 h (a2) radioimaging of melanoma-bearing mice after injection with 188 Re-T 3,4 CPP [1]; (M) Acoustic images of a tumor-bearing mouse after injection with porphyrin-shell microbubbles [19]; (N) Image-guided surgery with a porphyrin-PEG cross-linked hydrogel [20]; (O) Phosphorescence images of an implanted Pd-porphyrin hydrogel in mice breathing different oxygen levels [13]; (P) Photoirradiation of bacteria under various photosensitizer conditions [21]; (Q) Photoimmunotherapy concept [22]. All figures used with permission from the indicated references.…”

Polymeric multifunctional nanomaterials for theranostics

“…The strategies used in advanced theranostics, such as polymer conjugations, solid lipid nanoparticles, dendrimers, micelles, magnetic nanoparticles, silica nanoparticles, and quantum dots, may achieve fewer side effects and better synergistic outcomes 8,9 . The goal of theranostics is to diagnose and treat a disease at its earliest stage.…”