conclude, yet been developed. Great progress did attained

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nanodiamonds-based anticancer therapies demonstrate a great promise, opening
many new exciting avenues. For example, recent progress in inducing vascular
leakiness will potentially help to deliver higher concentrations of chemotherapeutics to tumors in early stages of
tumorigenesis, when the EPR effect has not yet been developed. Great progress did attained in delivering poorly
water-soluble anticancer drugs by means
of nanodiamonds platforms. The ND large and tunable surface allows one to
adsorb and sustainably release anticancer therapeutics in response to pH change
and other stimuli. Nanodiamonds -drug adsorption complexes have shown great
promise in killing drug-resistant cancer,
by passing drug efflux and reducing side effects of
anticancer drugs. Also, nanodiamonds -drug adsorption complexes have been used
in combination therapy as a part of efficient drug cocktails to treat multidrug-resistant tumors and fight
migrating cancer stem cells causing metastases. There is great hope that these
exciting successes of nanodiamonds in fighting cancer can soon be translated
to clinics. Taking into account the negligible toxicity of nanodiamonds, low
cost and available commercial production, nanodiamonds meets all criteria to an
excellent anticancer theranostic platform.

       Nanodiamonds with the positive charge can form
complexes with nucleic acids and help as a gene delivery vectors. A positive
charge on the nanodiamonds surface generate from a
positively charged polymer, such as PEI, adsorbed on the surface. Nanodiamonds -PEI conjugates with siRNA were
able to ruin the target mRNA, resulting in oncogene silencing when internalized
by macropinocytosis. In another study, DNDs with
a PEI-modified surface formed a complex with siRNA used for knocking down the
gene for green fluorescent protein. Methacrylate derivatives with chargeable
nitrogen in a side chain grown from the DND surface can deliver plasmids into
cells and mediate higher decleration than PEI (25 kDa) with lower cytotoxicity228–230. Stable PG-coated  nanodiamonds can be converted into positively charged NPs by a
multistep reaction with the basic polypeptides Arg8 or Lys8. This architecture
is able to complex with plasmid DNA, offering the potential to act as agene
vector. Recently, it was shown that DNDs do not require to be coated by
polymers for nucleic acid complexation. Polymers increase the size of the NP,
and when the polymer is noncovalently bound to the nanodiamonds vector, it may dissociate from
its surface. Positively charged hydrogenated detonated nanodiamonds also showed a capacity to
complex with siRNA and deliver it into cells to inhibit the target gene. As
charged molecules, peptide or protein can be loaded onto the surface of nanodiamonds, since their surface elements
such as anionic end groups (–COO?) and protonated amino groups
(–NH+3) gives the favourable
conditions for charge-charge interaction
with nanodiamonds.
Meanwhile, hydrogen bonds may exist between ND and these biomolecules to
improve the adsorption231–233.

example of directly loading proteins on nanodiamonds have been reported   where
the bovine insulin was non-covalently bound to nanodiamonds via physical adsorption in an
aqueous solution234. Although insulin presents a
slightly negative net charge at neutral pH, the adsorption was still completed,
indicating that loading process may include both electrostatic interaction and
H-binding. Meanwhile, insulin can be released from the ND-insulin complex in
basic condition (Fig.6), which can be described by the change in charge
characteristics that is affected by pH modification. It was concluded that
exposure of the nanodiamonds -insulin complex to alkaline
environment mediates the interaction between the NDs and insulin, resulting in
protein liberation235.

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