br transactivating growth related genes and suppressing
transactivating growth-related genes and suppressing specific target genes but also possesses anti-apoptosis capability to tolerate che-motherapeutic drugs such as doxorubicin (DOX) [10,11]. Even though treated with high doses of DOX, the cancer APTSTAT3-9R growth still can’t be inhibited. Meanwhile, normal cells and tissues also suffer from the serious drug side effects. The mutant p53 in resistant human breast cancer cells (MCF-7/ADR) is four to six times the level of it in human breast cancer cells (MCF-7) . Thus, the treatment target to decrease the mutant p53 levels in resistant cancer cells would be one of the ef-ficient way to reduce MDR.
Phenethyl isothiocyanate (PEITC) derived from cruciferous vege-tables such as broccoli, cabbage, and watercress, can selectively deplete
E-mail addresses: firstname.lastname@example.org (N. Zhou), email@example.com (X. Yi).
mutant p53 but not the wild-type . Thus, the nano-drug delivery system integrated with PEITC may be a new strategy for reversing MDR. Two-dimensional (2D) nanomaterials with unique physicochemical properties have become one of the most pop research fields of na-noscale science and technology [12–14]. Its huge diversity of applica-tions has been presented, such as electronics , catalysis , op-toelectronics , energy conversion and storage [18,19], and biomedicine [20,21]. In particular, 2D nanomaterials-based nano-drug delivery systems for cancer treatment have been received a lot of at-tention [22–25]. However, some shortcomings restrict the utility of these nanomaterials, such as graphene cannot be used as photo-sensitizer to generate reactive oxygen species (ROS) for photodynamic therapy (PDT) , and the low drug loading capacity of WS2 , C3N4 , and MoS2 . Compared to these 2D nanomaterials, black phosphorus (BP) as effective photosensitizers for PDT presents a high drug loading capacity due to its puckered lattice configuration which enhance surface area-to-volume ratio [30–33]. In addition, BP can also be used as photothermal agent to transform near infrared (NIR) light into heat for photothermal therapy (PTT) [34–36]. BP has distinct structure with corrugated planes of P atoms, which are connected by strong interlayer P-P bonding and weak interlayer van der Waals forces . The bulk BP can be exfoliated to single-layer or few-layer BP nanosheets (BPNs) through destroying the weak interlayer forces [38,39]. However, BPNs can’t be directly integrated with PEITC due to the lack of reactive functional groups in BPNs surface. Mussels have strong adhesive interactions with diverse substrates even in wet con-ditions, due to the reactive 3,4-dihydroxy-l-phenylalanine (DOPA) and lysine . According to this property, polydopamine (PDA) which has a similar molecular structure with DOPA was used to modify various material surfaces, such as biomedical metal materials [41,42], polymer films , and nanocarriers [7,44–49]. In specific conditions, dopa-mine undergoes oxidative self-polymerization, and the PDA layer can be deposited on nearly various material surfaces. PDA layer has abun-dant groups which can bind with many functional molecules.
Herein, a multifunctional BPNs-based drug delivery system was established (Scheme 1). DOX with positive charge, a normal che-motherapy drug used in clinic, which could intercalate in the DNA base pairs and block the replication activities in the cancer cell to achieve cell apoptosis, could be encapsulated in BPNS (BPNs/DOX) by means of electrostatic interaction . BPNs/DOX was coated PDA layer (BPNs-PDA/DOX) through dopamine polymerization method . Poly-ethylene glycol–amine (PEG-NH2) react with PDA layer via Schiff base reaction (BPNs-PDA-PEG/DOX) . PEG could enhance the solubility and stability of nanosheets in physiological environments and realize the passive targeting tumor . BPNs-PDA-PEG/DOX was decorated with PEITC (BPNs-PDA-PEG-PEITC/DOX) via π-π stacking which can decrease mutant p53 levels and enhance chemotherapy drug sensi-tiveness . Furthermore, the phenolic hydroxyl groups of BPNs-PDA-PEG-PEITC/DOX chelate manganese ion (Mn2+) (BPNs-PDA-PEG-PEITC-Mn/DOX) which exhibit a strong T1 contrast in magnetic re-sonance imaging (MRI) . Thus, the BPNs-PDA-PEG-PEITC-Mn/DOX could be used as the theranostic agent used for MRI-guided PTT/PDT/ chemo-therapy synergistic drug-resistant cancer therapy. This work demonstrates that BPNs-based nanocomposite exhibit excellent anti-tumor effect on resistant tumor with little side effect which could be used as a promising nanoplatform for resistant cancer theranostics.
2. Results and discussion
2.1. Preparation and characterization of samples