Development and bioevaluation of controlled release 5-aminoisoquinoline nanocomposite: a synergistic anticancer activity against human colon cancer

Alaa AL-Rahman Gamal; El-Sayed Mahmoud El-Sayed; Tarek El-Hamoly; Heba Kahil; Alaa AL-Rahman Gamal; El-Sayed Mahmoud El-Sayed; Tarek El-Hamoly; Heba Kahil

doi:10.3934/biophy.2022003

AIMS Biophysics

2022, Volume 9, Issue 1: 21-41. doi: 10.3934/biophy.2022003

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Development and bioevaluation of controlled release 5-aminoisoquinoline nanocomposite: a synergistic anticancer activity against human colon cancer

1.
Biophysics group, Physics Department, Faculty of Science, Ain Shams University, Cairo Egypt
2.
Drug Radiation Research Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt
3.
Cyclotron Project, Nuclear Research Centre, Egyptian Atomic Energy Authority, Cairo, Egypt

Received: 16 November 2021 Revised: 04 February 2022 Accepted: 13 February 2022 Published: 25 February 2022

The current study presents a bimodal therapeutic platform for cancer treatment. Bimodal implies that the presented drug loaded core-shell structure is capable of elevating the tumor tissue temperature (hyperthermia) through the superparamagnetic iron oxide core and simultaneously release a Poly (ADP-ribose) polymerase-1(PARP-1)-modifying agent from the thermoresponsive shell. Magnetic thermoresponsive nanocomposite MTN was synthesized via an in situ free radical polymerization of thermo-responsive (N-isopropylacrylamide) (NIPAAm) monomer in the presence of 11-nm monodisperse SPIONs. The composite was allowed to swell in various concentrations of the PARP inhibitor: 5-aminoisoquinoline (5-AIQ) forming drug-loaded magnetic thermoresponsive nanocomposite (MTN-5.AIQ). Structural characterization of the formed composite is studied via various experimental tools. To assess the coil to globule transition temperature, the lower critical solution temperature (LCST) is determined by differential scanning calorimetry (DSC) method and the cloud point (Tp) is determined by turbidometry. Magnetic thermoresponsive nanocomposite (MTN) is formed with excellent potential for hyperthermia. A high drug loading efficiency (85.72%) is obtained with convenient temperature dependent drug release kinetics. Biocompatibility and cytotoxic efficacy are tested on an in vivo and in vitro colorectal-adenocarcinoma model, respectively. MTN.5-AIQ administration exhibits normal hepatic and renal functions as well as lower toxic effect on normal tissue. In addition, the composite effectively inhibits Caco-2 cells viability upon incubation. Based on the obtained results, the proposed therapeutic platform can be considered as a novel, promising candidate for dual therapy of colorectal adenocarcinoma exhibiting a PARP-1 overexpression. as well as increased the inhabiting efficacy of 5-AIQ.
- SPIONs,
- thermoresponsive polymer,
- hyperthermia,
- PARP inhibitor,
- PNIPAM
Citation: Alaa AL-Rahman Gamal, El-Sayed Mahmoud El-Sayed, Tarek El-Hamoly, Heba Kahil. Development and bioevaluation of controlled release 5-aminoisoquinoline nanocomposite: a synergistic anticancer activity against human colon cancer[J]. AIMS Biophysics, 2022, 9(1): 21-41. doi: 10.3934/biophy.2022003

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Abstract

The current study presents a bimodal therapeutic platform for cancer treatment. Bimodal implies that the presented drug loaded core-shell structure is capable of elevating the tumor tissue temperature (hyperthermia) through the superparamagnetic iron oxide core and simultaneously release a Poly (ADP-ribose) polymerase-1(PARP-1)-modifying agent from the thermoresponsive shell. Magnetic thermoresponsive nanocomposite MTN was synthesized via an in situ free radical polymerization of thermo-responsive (N-isopropylacrylamide) (NIPAAm) monomer in the presence of 11-nm monodisperse SPIONs. The composite was allowed to swell in various concentrations of the PARP inhibitor: 5-aminoisoquinoline (5-AIQ) forming drug-loaded magnetic thermoresponsive nanocomposite (MTN-5.AIQ). Structural characterization of the formed composite is studied via various experimental tools. To assess the coil to globule transition temperature, the lower critical solution temperature (LCST) is determined by differential scanning calorimetry (DSC) method and the cloud point (Tp) is determined by turbidometry. Magnetic thermoresponsive nanocomposite (MTN) is formed with excellent potential for hyperthermia. A high drug loading efficiency (85.72%) is obtained with convenient temperature dependent drug release kinetics. Biocompatibility and cytotoxic efficacy are tested on an in vivo and in vitro colorectal-adenocarcinoma model, respectively. MTN.5-AIQ administration exhibits normal hepatic and renal functions as well as lower toxic effect on normal tissue. In addition, the composite effectively inhibits Caco-2 cells viability upon incubation. Based on the obtained results, the proposed therapeutic platform can be considered as a novel, promising candidate for dual therapy of colorectal adenocarcinoma exhibiting a PARP-1 overexpression. as well as increased the inhabiting efficacy of 5-AIQ.

Abbreviations

5-AIQ

5-aminoisoquinoline

AMF

Alternating magnetic field

EDX

Energy dispersive X-ray

FCC

Face centered cubic

FTIR

Fourier transform infrared spectroscopy

GOT

Glutamic oxaloacetic transaminase

GPT

Glutamic pyruvic transaminase

HPLC

High performance liquid chromatography

HRTEM

High resolution transmission electron microscope

LCST

Lower critical solution temperature

MTN

Magnetic thermoresponsive nanocomposite

PARP-1

Poly (ADP-ribose) polymerase-1

PNIPAAm

Poly(N-isopropylacrylamide)

SAR

Specific absorption rate

SPIONs

Superparamagnetic iron oxide nanoparticles

T_CP

Cloud point temperature

XRD

X-ray diffraction

Acknowledgments

Magnetic and SAR measurements were conducted at Cyclotron Project, Nuclear Research Center, Egyptian Atomic Energy Authority, Egypt by Dr. Ismaeel Abdulrahim.

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest. Funding: The author(s) declared that no grants were involved in supporting this work. All in vivo experiments were conducted according to (ARRIVE) guidelines for animal care. All animal experiments were approved by the Ain Shams University Research Ethics Committee. The preliminary version of this work was posted in Research Square server as a preprint [46]. Availability of data and material: Additional datasets used in the present work are available from the corresponding author upon request.

Author contributions

Conceptualization: AAG, TE, HK; EME; data curation: AAG, HK; formal analysis: AAG, TE, HK; funding acquisition: AAG, TE, HK; investigation: AAG, TE; methodology: AAG, TE, HK; writing original draft preparation: AAG, EME; writing/review and editing: all authors. All authors read and approved the final manuscript.

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