Triangular Gold Nanoprism Based Theranostics For Breast Cancer

Breast cancer is one of the most common malignancy among women all over the world and constitutes an enormous burden on society.The current first-line breast cancer treatment modalities,such as surgery,chemotherapy,and radiation therapy,always cause serious side effects.Thus,it is of great need to develop novel theraputic modalities for efficient breast cancer treatment with minimized side effects.Phototherapy(PTT)mediated by gold nanostructures holds promise in the area of anti-tumour therapy for its precise energy delivery,minimal invasion,and highly spatiotemporal selectivity.Gold nanostructures based cancer theranostics combines single or multiple imaging modalities with phototherapy and integration of lesion detection,cancer treatment and therapeutic efficacy monitoring within a single nanoplatform could dramatically simplify and optimize the tumour diagnosis and treatment.We designed two novel nanoplatforms based on gold nanoprism for breast cancer imaging and treatment,including:1.Timely-Coordinated Phototherapy Mediated by Mesoporous Organosilica Coated Triangular Gold NanoprismFor the first time,we constructed a novel nanocomposite(TGP@MOS)with mesoporous organosilica shell and triangular gold nanoprism core.To obtain the benzene-bridged mesoporous organosilica shell,the aromatic compound 1,4-bis(triethoxysily)benzene(BTSB)was chose as precursor.Via π-π stacking or hydrophobic interaction mediated by the polyaromatic silica shell,we effectively loaded the ZnPc(denoted as TGP@MOS-ZnPc),one photosensitizer with poor water solubility.As compared with the mesoporous inorganic silica nanoshell coated triangular gold nanoprism(TGP@MSN),TGP@MOS was able to load ZnPc with much higher loading capacity up to 11.8 wt%.Through this loading strategy,the 1O2 generating ability of ZnPc was largely retained(79.5%),which efficiently enables TGP@MOS-ZnPc with photodynamic effect.Moreover,TGP@MOS-ZnPc showed excellent colloidal stability in bioenvironment with the ZnPc premature release of less than 3%.The triangular gold nanoprism was chosen as the inner core for its ultrahigh photothermal conversion efficacy(η≈70%)and the localized surface plasmon resonance(LSPR)properties of TGP were adapted to match the absorption peak of ZnPc.Upon laser irradiation,the loaded ZnPc molecules produced singlet oxygen expeditiously,providing efficient photodynamic treatment.Over time,the temperature of TGP component rises and the corresponding photothermal effect cumulatively increases.Since the photothermal effect is not oxygen-dependent like PDT,the late-phase PTT could balance the attenuation of photodynamic effect from rapid oxygen consumption and photobleaching of ZnPc under irradiation,thus ensuring the high therapeutic efficacy during the whole treatment course.We verified this time-synergetic effect could dramatically enhance the therapeutic effect of phototherapy for breast cancer both in vitro and in vivo.Other advantages of TGP@MOS-ZnPc include excellent water solubility,stability,hemo-and biocompatibility.2.T1-Weighted MR/CT Dual-Modality Imaging Guided Photothermal Therapy Using Gadolinium Functionalized Triangular Gold NanoprismIn this work,a gadopentetic acid(Gd-DTPA)decorated triangular gold nanoprism(TGP-PEG-Gd)was constructed for cancer theranostics.The TGP-PEG-Gd exhibits uniform morphology,excellent monodispersity and near infrared absorbance ability.The magnetic property of gadolinium,together with the X-ray attenuation of gold,enable the TGP-PEG-Gd with T1-weighted MR/CT dual-modality imaging capacity.The longitudinal relaxivity(ri)of the TGP-PEG-Gd was calculated to be 23.1 mM-1 s-1,and the X-ray absorption coefficient was 959.3 HU L g-1.Meanwhile,the TGP-PEG-Gd possesses effective photothermal conversion ability and high photothermal conversion efficacy of 68.9%,which was utilized for powerful photothermal therapy.Moreover,the excellent biocompatibility of TGP-PEG-Gd was proved both in vitro and in vivo.The biocompatible TGP-PEG-Gd may hold promise for MR/CT dual-modality imaging-guided photothermal therapy of cancers.